The BRG1 transcriptional coregulator

Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina, USA.
Nuclear Receptor Signaling 02/2008; 6:e004. DOI: 10.1621/nrs.06004
Source: PubMed


The packaging of genomic DNA into chromatin, often viewed as an impediment to the transcription process, plays a fundamental role in the regulation of gene expression. Chromatin remodeling proteins have been shown to alter local chromatin structure and facilitate recruitment of essential factors required for transcription. Brahma-related gene-1 (BRG1), the central catalytic subunit of numerous chromatin-modifying enzymatic complexes, uses the energy derived from ATP-hydrolysis to disrupt the chromatin architecture of target promoters. In this review, we examine BRG1 as a major coregulator of transcription. BRG1 has been implicated in the activation and repression of gene expression through the modulation of chromatin in various tissues and physiological conditions. Outstanding examples are studies demonstrating that BRG1 is a necessary component for nuclear receptor-mediated transcriptional activation. The remodeling protein is also associated with transcriptional corepressor complexes which recruit remodeling activity to target promoters for gene silencing. Taken together, BRG1 appears to be a critical modulator of transcriptional regulation in cellular processes including transcriptional regulation, replication, DNA repair and recombination.

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    • "Finally, SWI/SNF chromatin remodeling complexes or CHD3 ATPases can associate with other chromatin regulatory complexes (e.g. Mi-2 NURD in mammals) that endow them with different activities (Trotter and Archer, 2008; Reynolds et al., 2013). "
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    ABSTRACT: Chromatin remodeling ATPases and their associated complexes can alter the accessibility of the genome in the context of chromatin by using the energy derived from ATP hydrolysis to change positioning, occupancy and composition of nucleosomes. In animals and plants, these remodelers have been implicated in diverse processes ranging from stem cell maintenance and differentiation to developmental phase transitions and stress responses. Detailed investigations of their roles in individual processes have suggested a higher level of selectivity of chromatin remodeling ATPase activity than previously anticipated and diverse mechanisms have been uncovered that can contribute to the selectivity. This review summarizes recent advances towards understanding the roles and activities of chromatin remodeling ATPases in plants. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    The Plant Journal 05/2015; 83(1). DOI:10.1111/tpj.12877 · 5.97 Impact Factor
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    • "Combinatorial assembly of six to eight additional BAFs confers specificity of function to individual SWI/SNF complexes (for review [1], [3]). Some SWI/SNF subunits can participate to other multiprotein complexes also involved in gene transcription regulation, such as N-CoR, WINAC, NUMAC and mSIN3A [2], [4]. SWI/SNF remodeling activity is involved in many physiological processes such as embryonic development, maintenance of pluripotency, cell reprogramming [5], cellular differentiation and pathological processes like tumorigenesis or neurological disorders [6], [7]. "
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    ABSTRACT: Myogenic terminal differentiation is a well-orchestrated process starting with permanent cell cycle exit followed by muscle-specific genetic program activation. Individual SWI/SNF components have been involved in muscle differentiation. Here, we show that the master myogenic differentiation factor MyoD interacts with more than one SWI/SNF subunit, including the catalytic subunit BRG1, BAF53a and the tumor suppressor BAF47/INI1. Downregulation of each of these SWI/SNF subunits inhibits skeletal muscle terminal differentiation but, interestingly, at different differentiation steps and extents. BAF53a downregulation inhibits myotube formation but not the expression of early muscle-specific genes. BRG1 or BAF47 downregulation disrupt both proliferation and differentiation genetic programs expression. Interestingly, BRG1 and BAF47 are part of the SWI/SNF remodeling complex as well as the N-CoR-1 repressor complex in proliferating myoblasts. However, our data show that, upon myogenic differentiation, BAF47 shifts in favor of N-CoR-1 complex. Finally, BRG1 and BAF47 are well-known tumor suppressors but, strikingly, only BAF47 seems essential in the myoblasts irreversible cell cycle exit. Together, our data unravel differential roles for SWI/SNF subunits in muscle differentiation, with BAF47 playing a dual role both in the permanent cell cycle exit and in the regulation of muscle-specific genes.
    PLoS ONE 10/2014; 9(10):e108858. DOI:10.1371/journal.pone.0108858 · 3.23 Impact Factor
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    • "One of these factors, SWI/SNF, is a large chromatin-remodeling complex that contains either BRG1 or BRM exclusively as the catalytic ATPase subunit that drives the alteration of DNA-nucleosome structure and thus regulates gene transcription (Fryer and Archer, 1998; Trotter and Archer, 2008; Wang et al., 1996). Previous studies revealed that deletions of BRG1 or core subunits of the SWI/ SNF complex, such as BAF155 and BAF47, led to peri-implantation lethality due to compromised survival of totipotent cells that give rise to both the inner cell mass and trophoblast, suggesting a requirement of the SWI/ SNF complex for totipotency in vivo (Bultman et al., 2005; Kim et al., 2001; Klochendler-Yeivin et al., 2000). "
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    ABSTRACT: The SWI/SNF complex plays an important role in mouse embryonic stem cells (mESCs), but it remains to be determined whether this complex is required for the pluripotency of human ESCs (hESCs). Using RNAi, we demonstrated that depletion of BRG1, the catalytic subunit of the SWI/SNF complex, led to impaired self-renewing ability and dysregulated lineage specification of hESCs. A unique composition of the BRG1-SWI/SNF complex in hESCs was further defined by the presence of BRG1, BAF250A, BAF170, BAF155, BAF53A, and BAF47. Genome-wide expression analyses revealed that BRG1 participated in a broad range of biological processes in hESCs through pathways different from those in mESCs. In addition, chromatin immunoprecipitation sequencing (ChIP-seq) demonstrated that BRG1 played a repressive role in transcriptional regulation by modulating the acetylation levels of H3K27 at the enhancers of lineage-specific genes. Our data thus provide valuable insights into molecular mechanisms by which transcriptional repression affects the self-renewal and differentiation of hESCs.
    Stem Cell Reports 09/2014; 3(3):460-74. DOI:10.1016/j.stemcr.2014.07.004 · 5.37 Impact Factor
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