Stem Cells International
Volume 2020 (2020), Article ID 8839703, 10 pages
https://doi.org/10.1155/2020/8839703

Review Article

ATP-Dependent Chromatin Remodeling Complex in the Lineage Specification of Mesenchymal Stem Cells

Wen Du,¹ Daimo Guo,² and Wei Du³

¹State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
²State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
³State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China

Correspondence should be addressed to Wei Du; weidu@scu.edu.cn

Received 11 July 2020; Revised 29 August 2020; Accepted 1 September 2020; Published 9 September 2020

Academic Editor: shuibin lin

Copyright © 2020 Wen Du et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Mesenchymal stem cells (MSCs) present in multiple tissues can self-renew and differentiate into multiple lineages including the bone, cartilage, muscle, cardiac tissue, and connective tissue. Key events, including cell proliferation, lineage commitment, and MSC differentiation, are ensured by precise gene expression regulation. ATP-dependent chromatin alteration is one form of epigenetic modifications that can regulate the transcriptional level of specific genes by utilizing the energy from ATP hydrolysis to reorganize chromatin structure. ATP-dependent chromatin remodeling complexes consist of a variety of subunits that together perform multiple functions in self-renewal and lineage specification. This review highlights the important role of ATP-dependent chromatin remodeling complexes and their different subunits in modulating MSC fate determination and discusses the proposed mechanisms by which ATP-dependent chromatin remodelers function.

1. Introduction

Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, are multipotent stromal cells that can differentiate into a variety of mesoderm cell types, including osteoblasts, chondrocytes, myocytes, and adipocytes [1–3]. MSCs are a heterogeneous subset of stem cells that can be obtained from different locations of adult tissues including the bone marrow, adipose tissue, and other sources [4–6]. Studies have also indicated that MSCs can differentiate into endoderm and ectoderm lineages, including hepatocytes, epidermal-like cells, neurons, and other cell fates [7–10]. MSCs are a great choice for tissue engineering, regenerative medicine, and clinical therapy. The MSC differentiation process is regulated by different regulatory mechanisms like signaling molecules and epigenetic modifications [11, 12]. All regulatory mechanisms determine the selective transcription of genes with discrete combinations. This selective transcription will define the differentiation process and subsequently determine the specific lineage. Knowledge of how specific lineage differentiation occurs and how epigenetic modifications are involved in this process will accelerate the research and development of cell-based tissue engineering therapy. The current review summarizes our understanding of how ATP-dependent chromatin remodeling complexes regulate multilineage MSC differentiation.

2. ATP-Dependent Chromatin Remodeling Complexes

Specific gene expression programs, which depend largely on the organization of the associated chromatin, define a variety of cellular processes like differentiation, proliferation, and stemness [13]. ATP-dependent chromatin alterations, as one of the major factors that affect chromatin state, can determine a specific gene’s transcription level [14–16]. ATP-dependent chromatin alteration is achieved by multisubunit ATP-dependent chromatin remodeling complexes. These complexes can utilize ATP hydrolysis-derived energy to remodel nucleosome structure, thus modulating transcription factor binding to cognate DNA.

ATP-dependent chromatin remodeling complexes mainly consist of an ATPase and multiple subunits. The ATPase subunit hydrolyzes ATP, while the associated subunits regulate ATPase catalytic activity and genome binding. Therefore, different combinations of ATPase and associated subunits result in various chromatin remodeling complexes with different functions [17, 18]. All ATP-dependent chromatin remodeling complexes include an ATPase subunit from the SNF2 family, which can be divided into four different subfamilies, including SWI/SNF (switch/sucrose nonfermentable), ISWI (imitation SWI), CHD (chromodomain helicase DNA-binding), and INO80 (SWI2/SNF2 related (SWR)) based on sequence similarity between their ATPase domains [16, 19, 20]. The diversity of different isoforms of associated subunits defines a variety of particular properties that are suited to the specific tissue type and assist in recruiting the complexes to specific genomic loci. Complexes with various subunit combinations have been detected in different cell or tissue types during development. For instance, the SWI/SNF complex with BAF60C of the BAF60 subunit functions in gene transcription in the muscles and the heart, while the BAF60A isoform of the complex has a limited role in these tissues [21, 22]. The increasingly identified tissue-specific subunits of ATP-dependent chromatin remodeling complexes indicate the necessity to better understand remodeler subunit composition and how they modulate tissue-specific gene transcription.

The interaction of ATP-dependent chromatin remodeling complexes and histone acetyltransferases (HATs) in gene transcription has been demonstrated. For example, the yeast Spt-Ada-Gcn5-acetyltransferase (SAGA) complex cooperates with the SWI/SNF complex via the cell wall integrity pathway for mandatory nucleosome displacement, which is essential for full gene expression [23]. It has also been found that the yeast and mammalian SWI/SNF complex is involved in the Rb/E2F pathway, which recruits SWI/SNF, histone deacetylases (HDACs), and histone methyltransferases (HMTs) to the E2F promoter that actively represses transcription [24]. In addition, SWI/SNF functions in both transcriptional activation and repression of the pS2 promoter via ligand-specific collaboration with HDAC1, P300, and prohibitin recruitment [25].

ATP-dependent chromatin remodeling complex can also cooperate with DNA methylation in various cellular processes. Several ATP-dependent chromatin remodeling enzymes, including the mammalian SNF2 family and ATPases ATRX and LSH (HELLS), are involved in DNA methylation at the fifth carbon of cytosine (5mC), which is an abundant epigenetic modification in vertebrate genomes [26–28]. The ATRX gene mutation, which resides on the X chromosome, causes a decrease of 30–60% in alpha globin gene expression, and this may result in an unusual form of thalassemia [27]. Patients with ATRX syndrome exhibit both hypermethylation and hypomethylation in highly repetitive elements, including satellite DNA, although the total 5mC level in the genome seems unchanged. However, a dramatic decrease (50%) in 5mC levels was present in LSH-null mice [28]. Fibroblasts from Lsh-/- mouse embryos, which lack DNA methylation from transposons, centromeric repeats, and several gene promoters, can reestablish DNA methylation and silence the misregulated genes with LSH reexpression [29]. The interactions between the complexes and other epigenetic regulation factors in different cell types provide a hint for investigating the potential role of ATP-dependent chromatin remodeling in multilineage MSC differentiation.

3. Role of ATP-Dependent Chromatin Remodeling in MSC Lineage Differentiation

3.1. SWI/SNF

The switch/sucrose nonfermentable (SWI/SNF) complex (also known as BAF) is composed of at least 15 different subunits that invariably include a core ATPase of either Brm (Brahma) or Brg1 (Brahma-related gene 1) that can provide the necessary energy to the complex for nucleosome remodeling activity [16]. BRM and BRG1 share 75% of amino acid sequences and have similar domains, including the ATPase domain, HSA domain (DNA binding), QLQ domain (protein-protein interaction), and bromodomain (acetyl-lysine histone mark recognition) [30]. Several common members including BAF155, BAF45A/B/C/D, BAF47, BAF53A/B, BAF57, BAF60A/B/C, and β-actin are shared by the complexes [31]. The BAF complexes can be divided into BAF250A-containing BAF-A complexes or BAF250B-containing BAF-B complexes depending on the combination of ATPase and associated subunits. Besides, BAF180- (polybromo-), BAF200-, and BRD7-containing complexes connected to the BRG1 ATPase subunit can form a polybromo-associated BAF (PBAF) complex [32].

Targeting of SWI/SNF to genomic sites is partly modulated via interactions of its associated subunits with transcription factors, histone modifications, and noncoding RNAs (ncRNAs), which were recently described. One example is the interaction between long ncRNA (lncRNA) SChLAP1 and SMARCB1/SNF5. SChLAP1 is an aberrantly expressed lncRNA identified in prostate cancer tissues [33], while SNF5 is a core subunit of the SWI/SNF complex that is essential for proper assembly and function of the complex [34]. Direct interaction has been found between SChLAP1 and SNF5 in human prostate cells, while SChLAP1 overexpression resulted in decreased SWI/SNF occupancy genome-wide [35].

SWI/SNF is critical for stem cell self-renewal and cell differentiation. BRG1, BAF47, and BAF155 depletion can impair the survival of totipotent cells and cause peri-implantation embryonic lethality in mice [36–38]. BRG1, BAF155, and BAF60A expressions are largely correlated with the reprogramming efficiency of induced pluripotent stem cells in the human population [39]. Some components of SWI/SNF have been involved in a transcriptional network that contains core transcription factors like OCT4, SOX2, and NANOG and maintains pluripotency in stem cells, and the Polycomb group (PcG) proteins modify chromatin to arrest differentiation [13, 40]. Deregulation of BRG1 expression induces MSC senescence with suppressed NANOG, and this is a part of the transcriptional circuitry that manages stem cell functions [41, 42]. BRG1 downregulation leads to an increase in DNA methyltransferase 1 (DNMT1) and Rb recruitment at the NANOG promoter, thus increasing methylation and transcriptionally silencing NANOG. BRG1 overexpression induces BRG1 occupancy at the NANOG promoter, thereby increasing chromatin compaction and recruiting HDACs [43]. Furthermore, BRG1 knockdown in hematopoietic stem cells and progenitors was shown to result in a compromised capacity of self-renewal both in vitro and in vivo [44].

Several studies have indicated that SWI/SNF is required for osteogenic induction (Table 1). Brg1 expression was detected in ex vivo osteoblast cultures and in skeletal tissues of mouse embryos [45]. This expression depends on the Runx2 expression induced by BMP2. The osteocalcin (OC) promoter region can recruit BRG1 via the transcription factor C/EBPβ; thus, BRG1 can induce OC expression regulated by RNA polymerase II [46]. Brg1 and P300 can also be recruited by Osterix (Osx) to its target gene promoter in vivo enhanced by p38 to form a complex that is transcriptionally active [47]. In addition, Brg1 and Baf47 can interact with C/EBPβ-LAP, which can bind to the Ric-8B promoter. This leads to Ric-8B expression downregulation in differentiating osteoblasts [48]. Several long-term osteogenic signals specifically upregulate the PBAF subunits BAF180, BAF200, and BRD7 in MSCs. The loss of Baf180/Baf200/Brd7 largely compromised the osteogenesis and osteolineage gene expression, while Baf180 loss was found to impair MSC ossification in vivo [49]. By comprehensive mapping, SWI/SNF complexes have also been identified in cartilage-expressed transcripts [50]. FGF receptor 3 (FGFR3) expression, which is critical for developing cartilage, can be induced by BMP2. This process is mediated by Sp1, a downstream mediator, and BRG1 can induce FGFR3 expression by selectively remodeling the Sp1 binding site-containing chromatin region that is located at the FGFR3 transcription start site [51].

Table 1: Types of ATP-dependent chromatin remodeling complexes and their subunits in different lineage specification.

Lineage
Types of ATP-dependent chromatin remodeling complexes

SWI/SNF
ISWI
CHD
INO80/SWR

Osteogenesis
BRG1, BAF47, BAF200, BAF180, BRD7

CHD1, CHD7, CHD9
INO80

Neurogenesis
BRG1, BAF45A, BAF53A, BAF53B
SNF2H, SNF2L
CHD4, CHD5, CHD7, CHD8

Adipogenesis
BRG1, BRM, BAF47

Cardiomyocytes
BRG1, BAF250A, BAF60C

CHD3, CHD4, CHD7

Hematopoiesis
BAF180, BAF45A
SNF2H, SNF2L
CHD1
P400

Hepatocytes
BRG1, BRM, BAF250A, BAF47, BAF60A

Chondrogenesis
BRG1

Muscle cells

ZNHIT1

ATP-dependent chromatin remodeling is also essential in promoter activation during adipogenic differentiation of MSCs. BRG1 and hBRM can cooperate with C/EΒPα, C/EΒPβ, C/EBPδ, and PPΑRγ2 to induce uncommitted fibroblasts into adipocytes [52, 53]. In 3T3-L1 preadipocytes and human MSCs, the depletion of BAF47 repressed adipogenic differentiation by interacting with PPARγ2 and C/EBPβ [54]. CARM1 or PRMT5, which are protein arginine methyltransferases, have also been found to mediate BRG1 binding to the PPARγ promoter [55–57]. In MSC cultures with the induction of adipocyte differentiation, BRG1 overexpression promoted the mature phenotypes that were connected with an obvious increase in the expression of the differentiation markers PPARγ and LPL [41]. Moreover, BRM plays an important role in maintaining the balance of MSC lineage selection between adipocytes and osteoblasts. For example, the depletion of BRM in MSCs favored the osteoblast lineage over the adipocyte lineage because BRM deletion in mice exhibited a rescued phenotype in age-related osteoporosis [58]. Furthermore, differentiated adipocytes have been found to exhibit increased miR-143 expression, while the application of antimiR-143 oligonucleotides could suppress differentiation [59]. miRNA378 expression is also relevant to adipocyte differentiation, and miRNA378 overexpression results in triglyceride accumulation and activation of lipogenic genes like PPARγ2 and GLUT4 [60]. This indicated the possibility that SWI/SNF cooperates with miRNAs to participate in adipogenic differentiation.

SWI/SNF is also important for hepatocyte differentiation. During early liver development, BRM or BRG1 can decrease the expression of tryptophan oxygenase, a gene specific to the late stage [61]. During hepatocyte differentiation, the BRM expression is upregulated by degrees while BRG1 is gradually decreased. BRM or BRG1 deficiency causes decreased albumin expression in hepatocytes because BRM and BRG1 can bind to the promoter region of the albumin gene and C/EBPα and RB family proteins [62]. BAF60A can upregulate PPARα target genes while stimulating β-oxidation of fat in hepatocytes [63]. Moreover, BAF47 deletion is accompanied by decreased levels of most genes involved in liver development [64]. On the other hand, the regeneration of the mammalian liver can be substantially improved by deleting Arid1a, a component of the SWI/SNF complexes. The loss of Arid1a leads to chromatin reprogramming that restricts promoter access by transcription factors like E2F4 and C/EBPα, which inhibit cell cycle reentry and enhance differentiation, respectively [65].

BRG1 is essential for regulating gene expression and the differentiation of cardiomyocytes [66]. In a mouse model, Brg1 deletion in the developing heart results in dysregulated cardiac gene expression and severe cardiac morphogenesis anomalies. By mediating remodeling of promoter chromatin and BRG1 recruitment, BAF250A regulates the expression of Mef2c, Nkx2-5, and Bmp10 during the differentiation of cardiac progenitor cells into beating cardiomyocytes [67]. In addition, BAF250A can interact with nucleosome remodeling and histone deacetylase (NURD), thus occupying the regulatory regions of genes associated with cardiomyocytes [68]. BAF250A is also critical in normal heart function, confirmed by BAF250A deletion in the sinoatrial node that stops Nkx2.5 repression, resulting in sick sinus diseases [69]. Moreover, BAF60C is crucial in reprogramming fibroblasts into cardiovascular precursors by interacting with other cardiac transcription factors, which indicates the important role of BAF60C in cardiac differentiation [70]. BAF60c can function together with Tbx5 and Gata4, the cardiomyocyte-specific transcription factors, to induce cardiomyocyte differentiation when Nodal/BMP signaling is suppressed [71]. Furthermore, BAF45A or BAF180 deficiency in mice results in hematopoietic system defects characterized by a decreased number of hematopoietic stem cells, impaired potential of long-term repopulating, and abnormal development of the hematopoietic lineage [72, 73].

MSCs could also differentiate into astrocytes or neurons when cultured with retinoic acid and neurotrophic factors derived from the brain [74]. Studies have shown that the deficiency of Brg1 and associated proteins resulted in neuronal disorders [75, 76]. During the differentiation of neurons, BAF53A is compromised and replaced by BAF53B, indicating the importance of SWI/SNF activity for proper neuron development [77]. Knockdown of Baf45a and/or Baf53a mediated by short hairpin RNA leads to decreased proliferation, while Baf45a overexpression improves neural progenitor cell mitosis. The SWI/SNF complex specific to neural progenitors regulates Notch and Shh signaling to promote proliferation and maintain the cells in the transition state from progenitors to postmitotic neurons [77]. Meanwhile, the depletion of BAF53B exhibits obvious defects in dendrite development and in memory [78]. Downregulated proliferation in neural progenitor cells with growth retardation in the cerebellum was also observed in mutations in Brg1 and some other SWI/SNF subunits in mice [79].

3.2. ISWI

ISWI complexes contain one of two conserved ATPase SMARCA5 (SNF2H) or SMARCA1 (SNF2L) along with two to four associated subunits [80]. The expression of Snf2h, which is critical for early embryonic development, is ubiquitous in various tissue types, while the Snf2l expression is restricted to the brain and postnatal reproductive tissues [80, 81]. Therefore, Snf2h loss leads to lethality, while mice with a Snf2l deficiency can still survive [82]. Furthermore, ISWI is required for nuclear organization and nucleosomal periodicity, and transcription factors depend upon specific remodeling pathways for proper genomic binding [83].

ISWI complexes containing either SNF2H or SNF2L are critical for ectoderm-derived lineage development [82, 84, 85]. In the nervous system, SNF2H is essential for neural progenitor proliferation, which can be partially compensated by SNF2L. Conditional Snf2h deletion compromises the proliferation of granule neuron progenitors and Purkinje cells with increased cell death, which leads to defects in postnatal neural maturation [84]. On the contrary, SNF2L was found to decrease the proliferation of neural progenitors to maintain the correct brain size. SNF2L also represses the expression of the transcription factor gene Foxg1 by binding to its promoter region. Therefore, SNF2L is required to maintain the balance between proliferation and differentiation of neural progenitors during brain development. This can be confirmed by the increased proliferation and self-renewal of neural progenitors in conditional Snf2l mutants accompanied by increased FOXG1 expression [82].

ISWI is also essential in mesoderm-derived lineage differentiation. The nucleosome remodeling factor (NURF) complex, which includes SNF2L-containing ISWI, plays an important role in erythropoiesis [81]. On the other hand, SNF2H is essential for hematopoietic progenitor proliferation at an early stage during erythropoiesis [81]. Therefore, the complexes with SNF2H or SNF2L function differently during the early and late stages of hematopoiesis. SNF2L-containing NURF is also required in thymocyte development [86]. Bromodomain PHD finger transcription factor (BPTF), one of the NURF subunits, is critical for CD4 or CD8 single-positive cells to differentiate into mature T cells by regulating DNase I hypersensitivity and cooperating with the transcription factor SRF to mediate the binding of NURF to Egr1, a gene specific to thymocyte maturation [86]. Bptf mutants were not able to differentiate any ectoderm, endoderm, or mesoderm tissue types, suggesting the important role of BPTF in germ layer formation. In addition, Bptf mutants failed to form distal ventral endoderm, and the expression of SMAD-responsive genes depended upon BPTF, suggesting that NURF functions as a transcription cofactor for SMAD [87]. SNF2L is also critical for granulosa cell proliferation and differentiation during folliculogenesis [88, 89]. Snf2l mutant mice responded differently under gonadotropin induction, and thus, they yielded significantly fewer eggs and exhibited fewer secondary follicles compared to control WT mice. The study also indicated that Fgl2 transcription, which can encode a prothrombinase for mouse reproduction to mediate folliculogenesis, is regulated by Snf2l [89].

Many genes are heterochromatinized upon differentiation, and thus, regularly spaced nucleosomes are needed for higher order compaction. The ISWI-containing chromatin remodeling complex ACF1 is required for nucleosome assembly. In the meantime, centromeric chromatin is assembled by RSF1, while heterochromatin formation is regulated by NoRC; thus, rDNA repeats can be silenced [90–92]. Deficiency in either Drosophila ISWI or BPTF leads to repressed histone H1 levels and a general male X chromosome decondensation [93, 94]. Therefore, ISWI-regulated histone H1 deposition and nucleosome spacing result in higher order chromatin structures and gene repression, which play an important role during the transition between the progenitor cell and the differentiated cell fate [95].

Taken together, ISWI complexes have been shown to have specific roles in cell proliferation, differentiation, or maturation (Table 1). SNF2H-containing ISWI complexes mainly participate in early development and progenitor cell proliferation, while the complexes containing SNF2L are mostly involved in cell differentiation and maturation.

3.3. CHD

Nine chromodomain helicase DNA-binding (CHD) proteins (CHD1-9), which can either function alone or cooperate with other proteins to form the complexes, constitute a CHD subfamily. Among them, different CHD complexes have distinct roles in early development and cell lineage differentiation.

CHD1 has been shown to be required for maintaining the self-renewal ability and pluripotency of embryonic stem cells [96, 97]. CHD1 was found to interact with RNA polymerases I/II to regulate the transcription of both rRNA and mRNA and maintain proper transcriptional output [98]. CHD1 is also involved in endothelial to hematopoietic transition (EHT), by which hematopoietic stem cells and progenitors derive from endothelial cells in various organs. However, CHD1 is not essential before or after hematopoietic stem cell and progenitor formation, and CHD1 functions to induce the high transcriptional output of hematopoietic progenitors only in a specific time window [99].

In the developing brain, the NuRD complex, which contains CHD4, is required for synapse formation [100]. This complex can compromise a set of developmentally downregulated genes in presynaptic granule neurons to drive synaptogenesis. However, CHD5 is involved in neuronal differentiation to inhibit nonneuronal lineage genes [101–103]. In addition, CHD7 is essential for maintaining the quiescence of neural stem cells in adults by repressing a number of cell cycle activators and inducing Notch signaling [104]. Moreover, CHD7 is critical for neurogenesis during the morphogenesis of the inner ear [105]. In contrast, CHD8 is associated with autism spectrum disorder (ASD). By decreasing half the dose of Chd8 in neural progenitor cells, the neural developmental genes containing those ASD-related genes were downregulated [106].

CHD complexes also play an important role in heart development. A NuRD complex containing CHD3 or CHD4 is involved in the proliferation of cardiomyocytes by interacting with the transcription factor FOG2 [107]. Once the interaction between FOG2 and NuRD is impaired, it may lead to perinatal lethality because of a thin ventricular myocardium and defects in the atrial and ventricular septum. The FOG2-NuRD interaction maintains cardiomyocyte proliferation by inhibiting Cdkn1a, which is a cell cycle inhibitor gene. Therefore, the disruption phenotype in the FOG2-NuRD interaction can be rescued through Cdkn1a deletion. Furthermore, CHD7 is involved in transcription activity in various heart development processes. Chd7 mutant mice exhibited CHARGE syndrome in cardiac aspects [108, 109] while CHD7 mutations have been discovered in sporadic cases in congenital human heart defects [110].

In a well-established MSC model with the induction of osteoblast lineage differentiation, CHD1 is essential for osteogenesis by regulating the transcriptional program of osteoblast differentiation, specifically at later stages. Moreover, CHD1 depletion was shown to reduce the induction of lineage-specific genes in adipocyte differentiation, indicating that CHD1 has a more general role in regulating transcriptional programs related to MSC differentiation [111]. CHD7 is also important in osteogenic differentiation since the expression of CHD7 can be induced in MSCs under osteogenic induction medium conditions while CHD7 depletion in MSCs leads to the repression of several osteogenic transcription factors and decreased MSC osteogenesis capability [112]. ChIP analysis showed that CHD9 can bind to skeletal tissue-specific promoters expressed at different stages during osteoprogenitor differentiation. The interactions between CHD9 and the promoter regions involved in the osteogenic process demonstrate the importance of CHD9 in the transcription process in osteoprogenitor cells and its possible role in the MSC maturation direction [113–115]. Another study indicated that nucleolar CHD9 acts as a ribosomal gene transcription regulator, which has also been implicated in cell fate and differentiation of MSCs [116].

Overall, CHD complexes function to regulate transcription or suppression of different genes and induce various lineage differentiations in MSCs (Table 1). This process relies on the cooperation of CHD complexes with histone modifiers and transcription factors specific to different lineages.

3.4. INO80/SWR

The ATPase subunits of INO80/SWR are another subfamily of ATP-dependent chromatin remodeling complexes that exhibit a conserved insertion in the ATPase/helicase domain. This is required for the interaction between RVB1/RVB2 helicase and these complexes [117]. The INO80 subfamily includes the INO80 complex [118], while SWR is comprised of P400/TIP60 and SRCAP [119]. Histone variant H2A.Z exchange and ATP-dependent nucleosome mobilization are present in INO80-involving chromatin remodeling [120]. However, SWR complexes are mostly required in the process of H2A.Z deposition into nucleosomes that contain H2A [117].

MSCs transfected with siRNAs targeting INO80 resulted in an impaired mineral deposition in osteogenic induction conditions, and the implanted mice with INO80-silencing MSCs also exhibited decreased bone formation. This suggests the essential role of the INO80 complex in MSC osteogenic differentiation and its potential application in tissue engineering in the clinic and osteoporosis treatment [121] (Table 1). INO80 is critical for meiotic recombination during spermatogenesis [122]. A conditional Ino80 mutation in spermatogonia before meiosis led to reduced synapse formation and double-strand break defects [123, 124]. P400 (EP400), the subunit of the SWR complex, plays an important role during hematopoiesis by regulating the expression of several embryonic globin genes and deregulating HOX gene expression [125, 126]. In bone marrow cells, P400 conditional knockout led to impaired stem and progenitor cell pool of hematopoiesis because of the progression defects in the cell cycle [125]. Moreover, P18Hamlet (ZNHIT1), a SRCAP subunit, is required for muscle differentiation [127]. P18Hamlet is phosphorylated at the promoter region of Myog, a muscle-specific transcription factor gene. H2A.Z is then recruited to phosphorylated P18Hamlet/SRCAP, forming the chromatin structure necessary for Myog transcription.

4. Conclusion

Over the past years, MSCs have become the focus of intense interest. Thus, they have been investigated for their capacities for self-renewal and lineage specification. The application of MSCs has been considered as a solution for the poor ability of adult tissue regeneration and a potential treatment for human diseases. Gene expression programs work at the chromatin level, so the organization of chromatin is essential in both normal and malignant development and tissue regeneration. We propose that the efficiency of differentiation of MSCs into a variety of cell types will be enhanced by modifying the composition of ATP-dependent chromatin remodeling complexes. As mentioned above, ATP-dependent chromatin remodeling complexes catalyze critical functions in self-renewal and multilineage differentiation of MSCs. In addition, the role of ATP-dependent chromatin remodeling in embryonic stem cells in diverse tissue types also raises the possibility that it may have similar functions in MSCs. The diversity of combinations of multiple subunits has specific functions in chromatin remodelers. For example, a specific combination plays an important role in ATP-dependent chromatin remodeling in differentiated cells, while another combination is crucial for some tissue progenitors. Moreover, ATP-dependent chromatin remodelers can regulate specific transcription in various cell types or with different transcriptional programs in the same cell type depending on the collaboration of these chromatin remodelers with histone-modifying complexes that can induce the binding of histone marks to regulatory sites. The insights of the ATP-dependent chromatin remodeling complexes and their roles in MSC fate determination will provide potential strategies for regeneration and cell-based tissue-engineering therapy.

Conflicts of Interest

The authors confirm that this article content has no conflicts of interest.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (NSFC) Grant 81900965 to Wei Du, SCU Postdoctoral Science Foundation (0040304153066 to Wei Du, 0040304153067 to Wen Du), and China Postdoctoral Science Foundation 0040304153062 to Wen Du.

References

J. A. Ankrum, J. F. Ong, and J. M. Karp, “Mesenchymal stem cells: immune evasive, not immune privileged,” Nature Biotechnology, vol. 32, no. 3, pp. 252–260, 2014.

R. S. Mahla, “Stem cells applications in regenerative medicine and disease therapeutics,” International Journal of Cell Biology, vol. 2016, Article ID 6940283, 24 pages, 2016.

A. I. Caplan, “Mesenchymal stem cells: time to change the name!,” Stem Cells Translational Medicine, vol. 6, no. 6, pp. 1445–1451, 2017.

Y. Jiang, B. N. Jahagirdar, R. L. Reinhardt et al., “Pluripotency of mesenchymal stem cells derived from adult marrow,” Nature, vol. 418, no. 6893, pp. 41–49, 2002.

M. Mohammadian, K. Shamsasenjan, P. Lotfi Nezhad et al., “Mesenchymal stem cells: new aspect in cell-based regenerative therapy,” Advanced Pharmaceutical Bulletin, vol. 3, no. 2, pp. 433–437, 2013.

L. L. Liau, B. H. I. Ruszymah, M. H. Ng, and J. X. Law, “Characteristics and clinical applications of Wharton's jelly-derived mesenchymal stromal cells,” Current Research in Translational Medicine, vol. 68, no. 1, pp. 5–16, 2020.

N. D. Theise, M. Nimmakayalu, R. Gardner et al., “Liver from bone marrow in humans,” Hepatology, vol. 32, no. 1, pp. 11–16, 2000.

Y. Lin, D. J. Weisdorf, A. Solovey, and R. P. Hebbel, “Origins of circulating endothelial cells and endothelial outgrowth from blood,” The Journal of Clinical Investigation, vol. 105, no. 1, pp. 71–77, 2000.

T. R. Brazelton, F. M. Rossi, G. I. Keshet, and H. M. Blau, “From marrow to brain: expression of neuronal phenotypes in adult mice,” Science, vol. 290, no. 5497, pp. 1775–1779, 2000.

D. Lo Furno, G. Mannino, and R. Giuffrida, “Functional role of mesenchymal stem cells in the treatment of chronic neurodegenerative diseases,” Journal of Cellular Physiology, vol. 233, no. 5, pp. 3982–3999, 2018.

A. Augello and C. De Bari, “The regulation of differentiation in mesenchymal stem cells,” Human Gene Therapy, vol. 21, no. 10, pp. 1226–1238, 2010.

Y. H. Cheng, J. C. Dong, and Q. Bian, “Small molecules for mesenchymal stem cell fate determination,” World Journal of Stem Cells, vol. 11, no. 12, pp. 1084–1103, 2019.

R. A. Young, “Control of the embryonic stem cell state,” Cell, vol. 144, no. 6, pp. 940–954, 2011.

J. W. Conaway, “Introduction to theme "chromatin, epigenetics, and transcription",” Annual Review of Biochemistry, vol. 81, no. 1, pp. 61–64, 2012.

B. Bartholomew, “Regulating the chromatin landscape: structural and mechanistic perspectives,” Annual Review of Biochemistry, vol. 83, no. 1, pp. 671–696, 2014.

S. K. Hota and B. G. Bruneau, “ATP-dependent chromatin remodeling during mammalian development,” Development, vol. 143, no. 16, pp. 2882–2897, 2016.

L. Ho and G. R. Crabtree, “Chromatin remodelling during development,” Nature, vol. 463, no. 7280, pp. 474–484, 2010.

J. I. Wu, J. Lessard, and G. R. Crabtree, “Understanding the words of chromatin regulation,” Cell, vol. 136, no. 2, pp. 200–206, 2009.

C. R. Clapier and B. R. Cairns, “The biology of chromatin remodeling complexes,” Annual Review of Biochemistry, vol. 78, no. 1, pp. 273–304, 2009.

D. C. Hargreaves and G. R. Crabtree, “ATP-dependent chromatin remodeling: genetics, genomics and mechanisms,” Cell Research, vol. 21, no. 3, pp. 396–420, 2011.

S. V. Forcales, S. Albini, L. Giordani et al., “Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex,” The EMBO Journal, vol. 31, no. 2, pp. 301–316, 2012.

H. Lickert, J. K. Takeuchi, I. von Both et al., “Baf60c is essential for function of BAF chromatin remodelling complexes in heart development,” Nature, vol. 432, no. 7013, pp. 107–112, 2004.

A. B. Sanz, R. Garcia, J. M. Rodriguez-Pena, C. Nombela, and J. Arroyo, “Cooperation between SAGA and SWI/SNF complexes is required for efficient transcriptional responses regulated by the yeast MAPK Slt 2,” Nucleic Acids Research, vol. 44, no. 15, pp. 7159–7172, 2016.

H. S. Zhang and D. C. Dean, “Rb-mediated chromatin structure regulation and transcriptional repression,” Oncogene, vol. 20, no. 24, pp. 3134–3138, 2001.

B. Zhang, K. J. Chambers, D. V. Faller, and S. Wang, “Reprogramming of the SWI/SNF complex for co-activation or co-repression in prohibitin-mediated estrogen receptor regulation,” Oncogene, vol. 26, no. 50, pp. 7153–7157, 2007.

M. M. Suzuki and A. Bird, “DNA methylation landscapes: provocative insights from epigenomics,” Nature Reviews. Genetics, vol. 9, no. 6, pp. 465–476, 2008.

R. J. Gibbons, T. L. McDowell, S. Raman et al., “Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation,” Nature Genetics, vol. 24, no. 4, pp. 368–371, 2000.

K. Dennis, T. Fan, T. Geiman, Q. Yan, and K. Muegge, “Lsh, a member of the SNF2 family, is required for genome-wide methylation,” Genes & Development, vol. 15, no. 22, pp. 2940–2944, 2001.

A. Termanis, N. Torrea, J. Culley, A. Kerr, B. Ramsahoye, and I. Stancheva, “The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells,” Nucleic Acids Research, vol. 44, no. 16, pp. 7592–7604, 2016.

L. Tang, E. Nogales, and C. Ciferri, “Structure and function of SWI/SNF chromatin remodeling complexes and mechanistic implications for transcription,” Progress in Biophysics and Molecular Biology, vol. 102, no. 2-3, pp. 122–128, 2010.

G. Euskirchen, R. K. Auerbach, and M. Snyder, “SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions,” The Journal of Biological Chemistry, vol. 287, no. 37, pp. 30897–30905, 2012.

Z. Yan, Z. Wang, L. Sharova et al., “BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells,” Stem Cells, vol. 26, no. 5, pp. 1155–1165, 2008.

J. R. Prensner, M. K. Iyer, O. A. Balbin et al., “Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression,” Nature Biotechnology, vol. 29, no. 8, pp. 742–749, 2011.

Y. Xu, W. Yan, and X. Chen, “SNF5, a core component of the SWI/SNF complex, is necessary for p53 expression and cell survival, in part through eIF4E,” Oncogene, vol. 29, no. 28, pp. 4090–4100, 2010.

J. R. Prensner, M. K. Iyer, A. Sahu et al., “The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex,” Nature Genetics, vol. 45, no. 11, pp. 1392–1398, 2013.

S. J. Bultman, T. C. Gebuhr, and T. Magnuson, “A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development,” Genes & Development, vol. 19, no. 23, pp. 2849–2861, 2005.

J. K. Kim, S. O. Huh, H. Choi et al., “Srg3, a mouse homolog of yeast SWI3, is essential for early embryogenesis and involved in brain development,” Molecular and Cellular Biology, vol. 21, no. 22, pp. 7787–7795, 2001.

A. Klochendler-Yeivin, L. Fiette, J. Barra, C. Muchardt, C. Babinet, and M. Yaniv, “The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression,” EMBO Reports, vol. 1, no. 6, pp. 500–506, 2000.

L. C. Mackey, L. A. Annab, J. Yang et al., “Epigenetic enzymes, age, and ancestry regulate the efficiency of human iPSC reprogramming,” Stem Cells, vol. 36, no. 11, pp. 1697–1708, 2018.

M. Li and J. C. Belmonte, “Ground rules of the pluripotency gene regulatory network,” Nature Reviews. Genetics, vol. 18, no. 3, pp. 180–191, 2017.

M. A. Napolitano, M. Cipollaro, A. Cascino, M. A. B. Melone, A. Giordano, and U. Galderisi, “Brg1 chromatin remodeling factor is involved in cell growth arrest, apoptosis and senescence of rat mesenchymal stem cells,” Journal of Cell Science, vol. 120, no. 16, pp. 2904–2911, 2007.

N. Alessio, T. Squillaro, M. Cipollaro, L. Bagella, A. Giordano, and U. Galderisi, “The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of mesenchymal stem cell senescence through RB-P53 pathways,” Oncogene, vol. 29, no. 40, pp. 5452–5463, 2010.

T. Squillaro, V. Severino, N. Alessio et al., “De-regulated expression of the BRG1 chromatin remodeling factor in bone marrow mesenchymal stromal cells induces senescence associated with the silencing of NANOG and changes in the levels of chromatin proteins,” Cell Cycle, vol. 14, no. 8, pp. 1315–1326, 2015.

C. Güneş, M. Paszkowski-Rogacz, S. Rahmig et al., “Comparative RNAi screens in isogenic human stem cells reveal SMARCA4 as a differential regulator,” Stem Cell Reports, vol. 12, no. 5, pp. 1084–1098, 2019.

D. W. Young, J. Pratap, A. Javed et al., “SWI/SNF chromatin remodeling complex is obligatory for BMP2-induced, Runx2-dependent skeletal gene expression that controls osteoblast differentiation,” Journal of Cellular Biochemistry, vol. 94, no. 4, pp. 720–730, 2005.

A. Villagra, F. Cruzat, L. Carvallo et al., “Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein beta-dependent recruitment of SWI/SNF activity,” The Journal of Biological Chemistry, vol. 281, no. 32, pp. 22695–22706, 2006.

M. J. Ortuño, S. Ruiz-Gaspà, E. Rodríguez-Carballo et al., “p38 regulates expression of osteoblast-specific genes by phosphorylation of osterix,” The Journal of Biological Chemistry, vol. 285, no. 42, pp. 31985–31994, 2010.

R. Aguilar, R. Grandy, D. Meza et al., “A functional N-terminal domain in C/EBPβ-LAP is required for interacting with SWI/SNF and to repress Ric-8B gene transcription in osteoblasts,” Journal of Cellular Physiology, vol. 229, no. 10, pp. 1521–1528, 2014.

S. Sinha, M. Biswas, S. S. Chatterjee, S. Kumar, and A. Sengupta, “Pbrm1 steers mesenchymal stromal cell osteolineage differentiation by integrating PBAF-dependent chromatin remodeling and BMP/TGF-β signaling,” Cell Reports, vol. 31, no. 4, p. 107570, 2020.

T. D. Yager, A. A. Dempsey, H. Tang et al., “First comprehensive mapping of cartilage transcripts to the human genome,” Genomics, vol. 84, no. 3, pp. 524–535, 2004.

F. Sun, Q. Chen, S. Yang et al., “Remodeling of chromatin structure within the promoter is important for bmp-2-induced fgfr3 expression,” Nucleic Acids Research, vol. 37, no. 12, pp. 3897–3911, 2009.

N. Salma, H. Xiao, E. Mueller, and A. N. Imbalzano, “Temporal recruitment of transcription factors and SWI/SNF chromatin-remodeling enzymes during adipogenic induction of the peroxisome proliferator-activated receptor gamma nuclear hormone receptor,” Molecular and Cellular Biology, vol. 24, no. 11, pp. 4651–4663, 2004.

J. Caramel, S. Medjkane, F. Quignon, and O. Delattre, “The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors,” Oncogene, vol. 27, no. 14, pp. 2035–2044, 2008.

S. E. LeBlanc, S. Konda, Q. Wu et al., “Protein arginine methyltransferase 5 (Prmt5) promotes gene expression of peroxisome proliferator-activated receptor γ2 (PPARγ2) and its target genes during adipogenesis,” Molecular Endocrinology, vol. 26, no. 4, pp. 583–597, 2012.

N. Yadav, D. Cheng, S. Richard et al., “CARM1 promotes adipocyte differentiation by coactivating PPARγ,” EMBO Reports, vol. 9, no. 2, pp. 193–198, 2007.

S. Pal, R. Yun, A. Datta et al., “mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad,” Molecular and Cellular Biology, vol. 23, no. 21, pp. 7475–7487, 2003.

W. Xu, H. Cho, S. Kadam et al., “A methylation-mediator complex in hormone signaling,” Genes & Development, vol. 18, no. 2, pp. 144–156, 2004.

K. H. Nguyen, F. Xu, S. Flowers, E. A. J. Williams, J. C. Fritton, and E. Moran, “SWI/SNF-mediated lineage determination in mesenchymal stem cells confers resistance to osteoporosis,” Stem Cells, vol. 33, no. 10, pp. 3028–3038, 2015.

N. Saidi, M. Ghalavand, M. S. Hashemzadeh, R. Dorostkar, H. Mohammadi, and A. Mahdian-shakib, “Dynamic changes of epigenetic signatures during chondrogenic and adipogenic differentiation of mesenchymal stem cells,” Biomedicine & Pharmacotherapy, vol. 89, pp. 719–731, 2017.

F. J. Ortega, J. M. Moreno-Navarrete, G. Pardo et al., “MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation,” PLoS One, vol. 5, no. 2, article e9022, 2010.

Y. Inayoshi, H. Kaneoka, Y. Machida et al., “Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development,” Journal of Biochemistry, vol. 138, no. 4, pp. 457–465, 2005.

Y. Inayoshi, K. Miyake, Y. Machida et al., “Mammalian chromatin remodeling complex SWI/SNF is essential for enhanced expression of the albumin gene during liver development,” Journal of Biochemistry, vol. 139, no. 2, pp. 177–188, 2006.

S. Li, C. Liu, N. Li et al., “Genome-wide coactivation analysis of PGC-1alpha identifies BAF60a as a regulator of hepatic lipid metabolism,” Cell Metabolism, vol. 8, no. 2, pp. 105–117, 2008.

L. Gresh, B. Bourachot, A. Reimann et al., “The SWI/SNF chromatin-remodeling complex subunit SNF5 is essential for hepatocyte differentiation,” The EMBO Journal, vol. 24, no. 18, pp. 3313–3324, 2005.

X. Sun, J. C. Chuang, M. Kanchwala et al., “Suppression of the SWI/SNF component Arid1a promotes mammalian regeneration,” Cell Stem Cell, vol. 18, no. 4, pp. 456–466, 2016.

J. K. Takeuchi, X. Lou, J. M. Alexander et al., “Chromatin remodelling complex dosage modulates transcription factor function in heart development,” Nature Communications, vol. 2, no. 1, 2011.

I. Lei, X. Gao, M. H. Sham, and Z. Wang, “SWI/SNF protein component BAF250a regulates cardiac progenitor cell differentiation by modulating chromatin accessibility during second heart field development,” The Journal of Biological Chemistry, vol. 287, no. 29, pp. 24255–24262, 2012.

A. P. Singh and T. K. Archer, “Analysis of the SWI/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation,” Nucleic Acids Research, vol. 42, no. 5, pp. 2958–2975, 2014.

M. Wu, S. Peng, J. Yang et al., “Baf250a orchestrates an epigenetic pathway to repress the Nkx2.5-directed contractile cardiomyocyte program in the sinoatrial node,” Cell Research, vol. 24, no. 10, pp. 1201–1213, 2014.

P. A. Lalit, M. R. Salick, D. O. Nelson et al., “Lineage reprogramming of fibroblasts into proliferative induced cardiac progenitor cells by defined factors,” Cell Stem Cell, vol. 18, no. 3, pp. 354–367, 2016.

W. Cai, S. Albini, K. Wei et al., “Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment,” Genes & Development, vol. 27, no. 21, pp. 2332–2344, 2013.

H. Lee, F. Dai, L. Zhuang et al., “BAF180 regulates cellular senescence and hematopoietic stem cell homeostasis through p21,” Oncotarget, vol. 7, no. 15, pp. 19134–19146, 2016.

V. Krasteva, G. R. Crabtree, and J. A. Lessard, “The BAF45a/PHF10 subunit of SWI/SNF-like chromatin remodeling complexes is essential for hematopoietic stem cell maintenance,” Experimental Hematology, vol. 48, pp. 58–71.e15, 2017, e15.

J. Sanchez-Ramos, S. Song, F. Cardozo-Pelaez et al., “Adult bone marrow stromal cells differentiate into neural cells in vitro,” Experimental Neurology, vol. 164, no. 2, pp. 247–256, 2000.

G. W. Santen, E. Aten, Y. Sun et al., “Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome,” Nature Genetics, vol. 44, no. 4, pp. 379-380, 2012.

Y. Tsurusaki, N. Okamoto, H. Ohashi et al., “Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome,” Nature Genetics, vol. 44, no. 4, pp. 376–378, 2012.

J. Lessard, J. I. Wu, J. A. Ranish et al., “An essential switch in subunit composition of a chromatin remodeling complex during neural development,” Neuron, vol. 55, no. 2, pp. 201–215, 2007.

A. Vogel-Ciernia, D. P. Matheos, R. M. Barrett et al., “The neuron-specific chromatin regulatory subunit BAF53b is necessary for synaptic plasticity and memory,” Nature Neuroscience, vol. 16, no. 5, pp. 552–561, 2013.

N. Moreno, C. Schmidt, J. Ahlfeld et al., “Loss of Smarc proteins impairs cerebellar development,” The Journal of Neuroscience, vol. 34, no. 40, pp. 13486–13491, 2014.

M. A. Lazzaro and D. J. Picketts, “Cloning and characterization of the murine Imitation Switch (ISWI) genes: differential expression patterns suggest distinct developmental roles for Snf2h and Snf2l,” Journal of Neurochemistry, vol. 77, no. 4, pp. 1145–1156, 2001.

T. Stopka and A. I. Skoultchi, “The ISWI ATPase Snf2h is required for early mouse development,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 24, pp. 14097–14102, 2011.

D. J. Yip, C. P. Corcoran, M. Alvarez-Saavedra et al., “Snf2l regulates Foxg1-dependent progenitor cell expansion in the developing brain,” Developmental Cell, vol. 22, no. 4, pp. 871–878, 2012.

D. Barisic, M. B. Stadler, M. Iurlaro, and D. Schubeler, “Mammalian ISWI and SWI/SNF selectively mediate binding of distinct transcription factors,” Nature, vol. 569, no. 7754, pp. 136–140, 2019.

M. Alvarez-Saavedra, Y. de Repentigny, P. S. Lagali et al., “Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation,” Nature Communications, vol. 5, no. 1, 2014.

D. Koludrovic, P. Laurette, T. Strub et al., “Chromatin-remodelling complex NURF is essential for differentiation of adult melanocyte stem cells,” PLoS Genetics, vol. 11, no. 10, article e1005555, 2015.

J. W. Landry, S. Banerjee, B. Taylor, P. D. Aplan, A. Singer, and C. Wu, “Chromatin remodeling complex NURF regulates thymocyte maturation,” Genes & Development, vol. 25, no. 3, pp. 275–286, 2011.

J. Landry, A. A. Sharov, Y. Piao et al., “Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells,” PLoS Genetics, vol. 4, no. 10, article e1000241, 2008.

M. A. Lazzaro, D. Pépin, N. Pescador, B. D. Murphy, B. C. Vanderhyden, and D. J. Picketts, “The imitation switch protein SNF2L regulates steroidogenic acute regulatory protein expression during terminal differentiation of ovarian granulosa cells,” Molecular Endocrinology, vol. 20, no. 10, pp. 2406–2417, 2006.

D. Pepin, F. Paradis, C. Perez-Iratxeta, D. J. Picketts, and B. C. Vanderhyden, “The imitation switch ATPase Snf2l is required for superovulation and regulates Fgl2 in differentiating mouse granulosa cells,” Biology of Reproduction, vol. 88, no. 6, p. 142, 2013.

D. V. Fyodorov, M. D. Blower, G. H. Karpen, and J. T. Kadonaga, “Acf1 confers unique activities to ACF/CHRAC and promotes the formation rather than disruption of chromatin in vivo,” Genes & Development, vol. 18, no. 2, pp. 170–183, 2004.

C. Guetg, P. Lienemann, V. Sirri et al., “The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats,” The EMBO Journal, vol. 29, no. 13, pp. 2135–2146, 2010.

M. Perpelescu, N. Nozaki, C. Obuse, H. Yang, and K. Yoda, “Active establishment of centromeric CENP-A chromatin by RSF complex,” The Journal of Cell Biology, vol. 185, no. 3, pp. 397–407, 2009.

P. Badenhorst, M. Voas, I. Rebay, and C. Wu, “Biological functions of the ISWI chromatin remodeling complex NURF,” Genes & Development, vol. 16, no. 24, pp. 3186–3198, 2002.

R. Deuring, L. Fanti, J. A. Armstrong et al., “The ISWI chromatin-remodeling protein is required for gene expression and the maintenance of higher order chromatin structure in vivo,” Molecular Cell, vol. 5, no. 2, pp. 355–365, 2000.

L. R. Goodwin and D. J. Picketts, “The role of ISWI chromatin remodeling complexes in brain development and neurodevelopmental disorders,” Molecular and Cellular Neurosciences, vol. 87, pp. 55–64, 2018.

A. Gaspar-Maia, A. Alajem, F. Polesso et al., “Chd1 regulates open chromatin and pluripotency of embryonic stem cells,” Nature, vol. 460, no. 7257, pp. 863–868, 2009.

P. Piatti, C. Y. Lim, R. Nat et al., “Embryonic stem cell differentiation requires full length Chd1,” Scientific Reports, vol. 5, no. 1, 2015.

M. Guzman-Ayala, M. Sachs, F. M. Koh et al., “Chd1 is essential for the high transcriptional output and rapid growth of the mouse epiblast,” Development, vol. 142, no. 1, pp. 118–127, 2014.

F. M. Koh, C. O. Lizama, P. Wong, J. S. Hawkins, A. C. Zovein, and M. Ramalho-Santos, “Emergence of hematopoietic stem and progenitor cells involves a Chd1-dependent increase in total nascent transcription,” Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 14, pp. E1734–E1743, 2015.

T. Yamada, Y. Yang, M. Hemberg et al., “Promoter decommissioning by the NuRD chromatin remodeling complex triggers synaptic connectivity in the mammalian brain,” Neuron, vol. 83, no. 1, pp. 122–134, 2014.

C. M. Egan, U. Nyman, J. Skotte et al., “CHD5 is required for neurogenesis and has a dual role in facilitating gene expression and polycomb gene repression,” Developmental Cell, vol. 26, no. 3, pp. 223–236, 2013.

P. M. Thompson, T. Gotoh, M. Kok, P. S. White, and G. M. Brodeur, “CHD5, a new member of the chromodomain gene family, is preferentially expressed in the nervous system,” Oncogene, vol. 22, no. 7, pp. 1002–1011, 2003.

A. Vestin and A. A. Mills, “The tumor suppressor Chd5 is induced during neuronal differentiation in the developing mouse brain,” Gene Expression Patterns, vol. 13, no. 8, pp. 482–489, 2013.

K. M. Jones, N. Sarić, J. P. Russell, C. L. Andoniadou, P. J. Scambler, and M. A. Basson, “CHD7 maintains neural stem cell quiescence and prevents premature stem cell depletion in the adult hippocampus,” Stem Cells, vol. 33, no. 1, pp. 196–210, 2015.

E. A. Hurd, H. K. Poucher, K. Cheng, Y. Raphael, and D. M. Martin, “The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear,” Development, vol. 137, no. 18, pp. 3139–3150, 2010.

A. Sugathan, M. Biagioli, C. Golzio et al., “CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 42, pp. E4468–E4477, 2014.

A. S. Garnatz, Z. Gao, M. Broman, S. Martens, J. U. Earley, and E. C. Svensson, “FOG-2 mediated recruitment of the NuRD complex regulates cardiomyocyte proliferation during heart development,” Developmental Biology, vol. 395, no. 1, pp. 50–61, 2014.

Y. Liu, C. Harmelink, Y. Peng, Y. Chen, Q. Wang, and K. Jiao, “CHD7 interacts with BMP R-SMADs to epigenetically regulate cardiogenesis in mice,” Human Molecular Genetics, vol. 23, no. 8, pp. 2145–2156, 2014.

S. Payne, M. J. Burney, K. McCue et al., “A critical role for the chromatin remodeller CHD7 in anterior mesoderm during cardiovascular development,” Developmental Biology, vol. 405, no. 1, pp. 82–95, 2015.

S. Zaidi, M. Choi, H. Wakimoto et al., “De novo mutations in histone-modifying genes in congenital heart disease,” Nature, vol. 498, no. 7453, pp. 220–223, 2013.

S. J. Baumgart, Z. Najafova, T. Hossan et al., “CHD1 regulates cell fate determination by activation of differentiation-induced genes,” Nucleic Acids Research, vol. 45, no. 13, pp. 7722–7735, 2017.

Y. Chen, M. Wang, D. Chen, J. Wang, and N. Kang, “Chromatin remodeling enzyme CHD7 is necessary for osteogenesis of human mesenchymal stem cells,” Biochemical and Biophysical Research Communications, vol. 478, no. 4, pp. 1588–1593, 2016.

I. Shur, R. Socher, and D. Benayahu, “In vivo association of CReMM/CHD9 with promoters in osteogenic cells,” Journal of Cellular Physiology, vol. 207, no. 2, pp. 374–378, 2006.

I. Shur, R. Solomon, and D. Benayahu, “Dynamic interactions of chromatin-related mesenchymal modulator, a chromodomain helicase-DNA-binding protein, with promoters in osteoprogenitors,” Stem Cells, vol. 24, no. 5, pp. 1288–1293, 2006.

D. Benayahu, N. Shacham, and I. Shur, “Insights on the functional role of chromatin remodelers in osteogenic cells,” Critical Reviews in Eukaryotic Gene Expression, vol. 17, no. 2, pp. 103–113, 2007.

R. Salomon-Kent, R. Marom, S. John et al., “New face for chromatin-related mesenchymal modulator: n-CHD9 localizes to nucleoli and interacts with ribosomal genes,” Journal of Cellular Physiology, vol. 230, no. 9, pp. 2270–2280, 2015.

G. Mizuguchi, X. Shen, J. Landry, W. H. Wu, S. Sen, and C. Wu, “ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex,” Science, vol. 303, no. 5656, pp. 343–348, 2004.

L. Chen, R. C. Conaway, and J. W. Conaway, “Multiple modes of regulation of the human Ino80 SNF2 ATPase by subunits of the INO80 chromatin-remodeling complex,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 51, pp. 20497–20502, 2013.

Y. Cai, J. Jin, L. Florens et al., “The mammalian YL1 protein is a shared subunit of the TRRAP/TIP60 histone acetyltransferase and SRCAP complexes,” The Journal of Biological Chemistry, vol. 280, no. 14, pp. 13665–13670, 2005.

M. Papamichos-Chronakis, S. Watanabe, O. J. Rando, and C. L. Peterson, “Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity,” Cell, vol. 144, no. 2, pp. 200–213, 2011.

C. Zhou, J. Zou, S. Zou, and X. Li, “INO80 is required for osteogenic differentiation of human mesenchymal stem cells,” Scientific Reports, vol. 6, no. 1, 2016.

D. W. Serber, J. S. Runge, D. U. Menon, and T. Magnuson, “The mouse INO80 chromatin-remodeling complex is an essential meiotic factor for spermatogenesis,” Biology of Reproduction, vol. 94, no. 1, p. 8, 2016.

D. Kato, M. Waki, M. Umezawa et al., “Phosphorylation of human INO80 is involved in DNA damage tolerance,” Biochemical and Biophysical Research Communications, vol. 417, no. 1, pp. 433–438, 2012.

I. Vassileva, I. Yanakieva, M. Peycheva, A. Gospodinov, and B. Anachkova, “The mammalian INO80 chromatin remodeling complex is required for replication stress recovery,” Nucleic Acids Research, vol. 42, no. 14, pp. 9074–9086, 2014.

T. Fujii, T. Ueda, S. Nagata, and R. Fukunaga, “Essential role of p400/mDomino chromatin-remodeling ATPase in bone marrow hematopoiesis and cell-cycle progression,” The Journal of Biological Chemistry, vol. 285, no. 39, pp. 30214–30223, 2010.

T. Ueda, R. Watanabe-Fukunaga, H. Ogawa et al., “Critical role of the p400/mDomino chromatin-remodeling ATPase in embryonic hematopoiesis,” Genes to Cells, vol. 12, no. 5, pp. 581–592, 2007.

A. Cuadrado, N. Corrado, E. Perdiguero, V. Lafarga, P. Muñoz-Canoves, and A. R. Nebreda, “Essential role of p18Hamlet/SRCAP-mediated histone H2A.Z chromatin incorporation in muscle differentiation,” The EMBO Journal, vol. 29, no. 12, pp. 2014–2025, 2010.