scholarly journals The Bromodomains of the mammalian SWI/SNF (mSWI/SNF) ATPases Brahma (BRM) and Brahma Related Gene 1 (BRG1) promote chromatin interaction and are critical for skeletal muscle differentiation

2020 ◽  
Author(s):  
Tapan Sharma ◽  
Hanna Witwicka ◽  
Anthony N. Imbalzano
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Skeletal Muscle ◽  
Muscle Differentiation ◽  
Chromatin Interaction ◽  
Specific Gene ◽  
Gene Promoters ◽  
Skeletal Muscle Differentiation ◽  
Chromatin Binding ◽  
Chip Analysis

ABSTRACTSkeletal muscle differentiation induces changes in the epigenome of myoblasts as they proceed towards a myogenic phenotype. mSWI/SNF chromatin remodeling enzymes coordinate with lineage-determining transcription factors and are key regulators of differentiation. Three mSWI/SNF proteins, the mutually exclusive ATPases, BRG1 and BRM, and the BAF180 protein (Polybromo1, PBRM1) contain bromodomains belonging to the same structural subfamily. Bromodomains bind to acetylated lysines on histone N-terminal tails and on other proteins. Pharmacological inhibition of mSWI/SNF bromodomain function using the selective inhibitor PFI-3 reduced differentiation, decreased expression of myogenic genes, and increased the expression of cell cycle-related genes, and the number of cells that remained in the cell cycle. Knockdown of BAF180 had no effect on differentiation, suggesting that only the BRG1 and BRM bromodomains contributed to differentiation. Comparison with existing gene expression data from myoblasts subjected to knockdown of BRG1 or BRM showed that bromodomain function was required for a subset of BRG1- and BRM-dependent gene expression. ChIP analysis revealed decreased BRG1 and BRM binding to target gene promoters, indicating that the BRG1 and BRM bromodomains promote chromatin binding. Thus mSWI/SNF ATPase bromodomains contribute to cell cycle exit, to skeletal muscle-specific gene expression, and to stable promoter binding by the mSWI/SNF ATPases.

scholarly journals Calcineurin Broadly Regulates the Initiation of Skeletal Muscle-Specific Gene Expression by Binding Target Promoters and Facilitating the Interaction of the SWI/SNF Chromatin Remodeling Enzyme

2019 ◽  
Vol 39 (19) ◽  
Author(s):  
Hanna Witwicka ◽  
Jumpei Nogami ◽  
Sabriya A. Syed ◽  
Kazumitsu Maehara ◽  
Teresita Padilla-Benavides ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Chromatin Remodeling ◽  
Regulation Of Gene Expression ◽  
Muscle Differentiation ◽  
Specific Gene ◽  
Skeletal Muscle Differentiation ◽  
Promoter Sequences ◽  
Cellular Processes ◽  
Nfat Transcription Factor

ABSTRACT Calcineurin (Cn) is a calcium-activated serine/threonine protein phosphatase that is broadly implicated in diverse cellular processes, including the regulation of gene expression. During skeletal muscle differentiation, Cn activates the nuclear factor of activated T-cell (NFAT) transcription factor but also promotes differentiation by counteracting the negative influences of protein kinase C beta (PKCβ) via dephosphorylation and activation of Brg1, an enzymatic subunit of the mammalian SWI/SNF ATP-dependent chromatin remodeling enzyme. Here we identified four major temporal patterns of Cn-dependent gene expression in differentiating myoblasts and determined that Cn is broadly required for the activation of the myogenic gene expression program. Mechanistically, Cn promotes gene expression through direct binding to myogenic promoter sequences and facilitating the binding of Brg1, other SWI/SNF subunit proteins, and MyoD, a critical lineage determinant for skeletal muscle differentiation. We conclude that the Cn phosphatase directly impacts the expression of myogenic genes by promoting ATP-dependent chromatin remodeling and formation of transcription-competent promoters.

scholarly journals The steroid receptor coactivator, GRIP-1, is necessary for MEF-2C-dependent gene expression and skeletal muscle differentiation

2000 ◽  
Vol 14 (10) ◽  
pp. 1209-1228 ◽  
Author(s):  
Shen Liang Chen ◽  
Dennis H. Dowhan ◽  
Brett M. Hosking ◽  
George E.O. Muscat
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Ectopic Expression ◽  
Steroid Receptor ◽  
Muscle Differentiation ◽  
C2c12 Cells ◽  
Bhlh Protein ◽  
Specific Gene ◽  
Skeletal Muscle Differentiation ◽  
Amino Terminal

Nuclear receptor-mediated activation of transcription involves coactivation by cofactors collectively denoted the steroid receptor coactivators (SRCs). The process also involves the subsequent recruitment of p300/CBP and PCAF to a complex that synergistically regulates transcription and remodels the chromatin. PCAF and p300 have also been demonstrated to function as critical coactivators for the muscle-specific basic helix–loop–helix (bHLH) protein MyoD during myogenic commitment. Skeletal muscle differentiation and the activation of muscle-specific gene expression is dependent on the concerted action of another bHLH factor, myogenin, and the MADS protein, MEF-2, which function in a cooperative manner. We examined the functional role of one SRC, GRIP-1, in muscle differentiation, an ideal paradigm for the analysis of the determinative events that govern the cell's decision to divide or differentiate. We observed that the mRNA encoding GRIP-1 is expressed in proliferating myoblasts and post-mitotic differentiated myotubes, and that protein levels increase during differentiation. Exogenous/ectopic expression studies with GRIP-1 sense and antisense vectors in myogenic C2C12 cells demonstrated that this SRC is necessary for (1) induction/activation of myogenin, MEF-2, and the crucial cell cycle regulator, p21, and (2) contractile protein expression and myotube formation. Furthermore, we demonstrate that the SRC GRIP-1 coactivates MEF-2C-mediated transcription. GRIP-1 also coactivates the synergistic transactivation of E box-dependent transcription by myogenin and MEF-2C. GST-pulldowns, mammalian two-hybrid analysis, and immunoprecipitation demonstrate that the mechanism involves direct interactions between MEF-2C and GRIP-1 and is associated with the ability of the SRC to interact with the MADS domain of MEF-2C. The HLH region of myogenin mediates the direct interaction of myogenin and GRIP-1. Interestingly, interaction with myogenic factors is mediated by two regions of GRIP-1, an amino-terminal bHLH–PAS region and the carboxy-terminal region between amino acids 1158 and 1423 (which encodes an activation domain, has HAT activity, and interacts with the coactivator-associated arginine methyltransferase). This work demonstrates that GRIP-1 potentiates skeletal muscle differentiation by acting as a critical coactivator for MEF-2C-mediated transactivation and is the first study to ascribe a function to the amino-terminal bHLH–PAS region of SRCs.

scholarly journals Enhancer of Polycomb1 Acts on Serum Response Factor to Regulate Skeletal Muscle Differentiation

2009 ◽  
Vol 284 (24) ◽  
pp. 16308-16316 ◽  
Author(s):  
Ju-Ryoung Kim ◽  
Hae Jin Kee ◽  
Ji-Young Kim ◽  
Hosouk Joung ◽  
Kwang-Il Nam ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Serum Response Factor ◽  
Muscle Differentiation ◽  
Specific Gene ◽  
Response Factor ◽  
Gene Promoters ◽  
Skeletal Muscle Differentiation ◽  
Actin Promoter ◽  
Myoblast Cells ◽  
Serum Response

Skeletal muscle differentiation is well regulated by a series of transcription factors. We reported previously that enhancer of polycomb1 (Epc1), a chromatin protein, can modulate skeletal muscle differentiation, although the mechanisms of this action have yet to be defined. Here we report that Epc1 recruits both serum response factor (SRF) and p300 to induce skeletal muscle differentiation. Epc1 interacted physically with SRF. Transfection of Epc1 to myoblast cells potentiated the SRF-induced expression of skeletal muscle-specific genes as well as multinucleation. Proximal CArG box in the skeletal α-actin promoter was responsible for the synergistic activation of the promoter-luciferase. Epc1 knockdown caused a decrease in the acetylation of histones associated with serum response element (SRE) of the skeletal α-actin promoter. The Epc1·SRF complex bound to the SRE, and the knockdown of Epc1 resulted in a decrease in SRF binding to the skeletal α-actin promoter. Epc1 recruited histone acetyltransferase activity, which was potentiated by cotransfection with p300 but abolished by si-p300. Epc1 directly bound to p300 in myoblast cells. Epc1+/− mice showed distortion of skeletal α-actin, and the isolated myoblasts from the mice had impaired muscle differentiation. These results suggest that Epc1 is required for skeletal muscle differentiation by recruiting both SRF and p300 to the SRE of muscle-specific gene promoters.

scholarly journals pRb is required for MEF2-dependent gene expression as well as cell-cycle arrest during skeletal muscle differentiation

1999 ◽  
Vol 9 (9) ◽  
pp. 449-459 ◽  
Author(s):  
Bennett G. Novitch ◽  
Douglas B. Spicer ◽  
Paul S. Kim ◽  
Wang L. Cheung ◽  
Andrew B. Lassar
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Skeletal Muscle ◽  
Cell Cycle Arrest ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Cycle Arrest

scholarly journals Calcineurin broadly regulates the initiation of skeletal muscle-specific gene expression by binding target promoters and facilitating the interaction of the SWI/SNF chromatin remodeling enzyme

2019 ◽  
Author(s):  
Hanna Witwicka ◽  
Jumpei Nogami ◽  
Sabriya A. Syed ◽  
Kazumitsu Maehara ◽  
Teresita Padilla-Benavides ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Chromatin Remodeling ◽  
Regulation Of Gene Expression ◽  
Muscle Differentiation ◽  
Specific Gene ◽  
Skeletal Muscle Differentiation ◽  
Promoter Sequences ◽  
Cellular Processes ◽  
Nfat Transcription Factor

ABSTRACTCalcineurin (Cn) is a calcium-activated serine/threonine protein phosphatase that is broadly implicated in diverse cellular processes, including the regulation of gene expression. During skeletal muscle differentiation, Cn activates the NFAT transcription factor but also promotes differentiation by counteracting the negative influences of protein kinase C beta (PKCβ) via dephosphorylation and activation of BRG1, an enzymatic subunit of the mammalian SWI/SNF ATP-dependent chromatin remodeling enzyme. Here we identified four major temporal patterns of Cn-dependent gene expression in differentiating myoblasts and determined that Cn is broadly required for the activation of the myogenic gene expression program. Mechanistically, Cn promotes gene expression through direct binding to myogenic promoter sequences and facilitating the binding of BRG1, other SWI/SNF subunit proteins, and MyoD, a critical lineage determinant for skeletal muscle differentiation. We conclude that the Cn phosphatase directly impacts the expression of myogenic genes by promoting ATP-dependent chromatin remodeling and formation of transcription-competent promoters.

scholarly journals Sarcosin (Krp1) in skeletal muscle differentiation: gene expression profiling and knockdown experiments

2012 ◽  
Vol 56 (4) ◽  
pp. 301-309 ◽  
Author(s):  
Leonie Du Puy ◽  
Abdelaziz Beqqali ◽  
Helena T.A. Van Tol ◽  
Jantine Monshouwer-Kloots ◽  
Robert Passier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Differentiation Gene

scholarly journals MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206

2006 ◽  
Vol 175 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Miriam I. Rosenberg ◽  
Sara A. Georges ◽  
Amy Asawachaicharn ◽  
Erwin Analau ◽  
Stephen J. Tapscott
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Cell Types ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Distinct Cell ◽  
Muscle Genes ◽  
Suppression Of Gene Expression ◽  
Dystrophin Protein

Terminal differentiation of distinct cell types requires the transcriptional activation of differentiation-specific genes and the suppression of genes associated with the precursor cell. For example, the expression of utrophin (Utrn) is suppressed during skeletal muscle differentiation, and it is replaced at the sarcolemma by the related dystrophin protein. The MyoD transcription factor directly activates the expression of a large number of skeletal muscle genes, but also suppresses the expression of many genes. To characterize a mechanism of MyoD-mediated suppression of gene expression, we investigated two genes that are suppressed in fibroblasts converted to skeletal muscle by MyoD, follistatin-like 1 (Fstl1) and Utrn. MyoD directly activates the expression of a muscle-specific microRNA (miRNA), miR-206, which targets sequences in the Fstl1 and Utrn RNA, and these sequences are sufficient to suppress gene expression in the presence of miR-206. These findings demonstrate that MyoD, in addition to activating muscle-specific genes, induces miRNAs that repress gene expression during skeletal muscle differentiation.

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