BAF60 A, B, and Cs of muscle determination and renewal
Mark Mercola2012, Genes & Development
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Abstract
Developmental biologists have defined many of the diffusible and transcription factors that control muscle differentiation, yet we still have only rudimentary knowledge of the mechanisms that dictate whether a myogenic progenitor cell forms muscle versus alternate lineages, including those that can be pathological in a state of disease or degeneration. Clues about the molecular basis for lineage determination in muscle progenitors are only now emerging from studies of chromatin modifications that avail myogenic genes for transcription, together with analysis of the composition and activities of the chromatin-modifying complexes themselves. Here we review recent progress on muscle determination and explore a unifying theme that environmental cues from the stem or progenitor niche control the selection of specific subunit variants of the switch/sucrose nonfermentable (SWI/SNF) chromatin-modifying complex, creating a combinatorial code that dictates whether cells adopt myogenic versus ...
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Journal of Biological Chemistry, 2002
The myogenic basic helix-loop-helix family of transcription factors, MyoD, Myf5, myogenin, and MRF4, can each activate the muscle differentiation program when ectopically expressed in non-muscle cells. SWI/SNF complexes are ATP-dependent chromatin remodeling enzymes. We demonstrated previously that SWI/SNF enzymes promote MyoD-mediated muscle differentiation. To ascertain the requirement for SWI/SNF enzymes in muscle differentiation mediated by different MyoD family members, we examined MyoD, Myf5, MRF4, and myogenin-mediated induction of muscle differentiation in cells expressing dominant negative versions of BRG1 or BRM-based SWI/SNF enzymes. We demonstrated that expression of dominant negative BRG1 or BRM inhibited the induction of muscle-specific gene expression by Myf5 and MRF4; however, myogenin failed to induce measurable quantities of muscle-specific mRNAs, even in cells not expressing dominant negative SWI/SNF. In contrast, all four myogenic regulators induced expression of the cell cycle regulators p21, Rb, and cyclin D3 and promoted cell cycle arrest independently of the SWI/SNF enzymes. We proposed that SWI/SNF enzymes are required for the induction of all muscle-specific gene expression by MyoD, Myf5, and MRF4, whereas induction of the cell cycle regulators, p21, Rb, and cyclin D3 occurred independently of SWI/SNF function.
Chromatin Landscape During Skeletal Muscle Differentiation
Frontiers in Genetics, 2020
Cellular commitment and differentiation involve highly coordinated mechanisms by which tissue-specific genes are activated while others are repressed. These mechanisms rely on the activity of specific transcription factors, chromatin remodeling enzymes, and higherorder chromatin organization in order to modulate transcriptional regulation on multiple cellular contexts. Tissue-specific transcription factors are key mediators of cell fate specification with the ability to reprogram cell types into different lineages. A classic example of a master transcription factor is the muscle specific factor MyoD, which belongs to the family of myogenic regulatory factors (MRFs). MRFs regulate cell fate determination and terminal differentiation of the myogenic precursors in a multistep process that eventually culminate with formation of muscle fibers. This developmental progression involves the activation and proliferation of muscle stem cells, commitment, and cell cycle exit and fusion of mononucleated myoblast to generate myotubes and myofibers. Although the epigenetics of muscle regeneration has been extensively addressed and discussed over the recent years, the influence of higher-order chromatin organization in skeletal muscle regeneration is still a field of development. In this review, we will focus on the epigenetic mechanisms modulating muscle gene expression and on the incipient work that addresses three-dimensional genome architecture and its influence in cell fate determination and differentiation to achieve skeletal myogenesis. We will visit known alterations of genome organization mediated by chromosomal fusions giving rise to novel regulatory landscapes, enhancing oncogenic activation in muscle, such as alveolar rhabdomyosarcomas (ARMS).
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Journal of Biological Chemistry, 2001
Cell cycle arrest is critical for muscle differentiation, and the two processes are closely coordinated but temporally separable. SWI/SNF complexes are ATP-dependent chromatin-remodeling enzymes that have been shown to be required for muscle differentiation in cell culture and have also been reported to be required for Rb-mediated cell cycle arrest. We therefore looked more closely at how SWI/SNF enzymes affect the events that occur during MyoD-induced myogenesis, namely, cell cycle regulation and muscle-specific gene expression, in cells that inducibly express dominant negative versions of Brahma (BRM) and Brahma-related gene 1 (BRG1), the ATPase subunits of two distinct SWI/SNF complexes. Although dominant negative BRM and BRG1 inhibited expression of every muscle-specific regulator and structural gene assayed, there was no effect on MyoD-induced activation of cell cycle regulatory proteins, and thus, cells arrested normally. In particular, in the presence or absence of dominant negative BRM or BRG1, MyoD was able to activate expression of p21, cyclin D3, and Rb, all of which are critical for cell cycle withdrawal in the G 1 /G 0 phase of the cell cycle. These findings suggest that at least one basis for the distinct mechanisms that regulate cessation of cell proliferation and musclespecific gene expression during muscle differentiation is that SWI/SNF-mediated chromatin-remodeling enzymes are required only for the latter.
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Nature Genetics, 2004
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The EMBO Journal, 2012
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FEBS Journal, 2014
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PLoS ONE, 2013
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2000
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MyoD is functionally linked to the silencing of a muscle-specific regulatory gene prior to skeletal myogenesis
Proceedings of the National Academy of Sciences, 2003
Most of the genes that are central to the process of skeletal muscle differentiation remain in a transcriptionally silent or ''off'' state until muscle cells (myoblasts) are induced to differentiate. Although the mechanisms that contribute to this phenomenon are still unclear, it is likely that histone deacetylases (HDACs), which play an important role in the repression of genes, are principally involved. Recent studies indicate that the initiator of the myogenic program, namely MyoD, can associate with the deacetylase HDAC1 in vivo, and because HDACs are usually recruited to promoters by specific proteins, we considered the possibility that these two proteins might be acting together at the promoters of musclespecific genes to repress their transcription in myoblasts. In this work, we show by chromatin immunoprecipitation (ChIP) assays that MyoD and HDAC1 are both occupying the promoter of myogenin and that this gene is in a region of repressed chromatin, as revealed by enrichment in histone H3 lysine 9 (Lys-9) methylation and the underacetylation of histones. Surprisingly, after the myoblasts are induced to differentiate, the promoter becomes absent of HDAC1, and eventually the acetyltransferase P͞CAF takes it place alongside MyoD. In addition, enrichment of histone H3 acetylation (Lys-9͞14) and phosphorylation of Ser-10 can now be observed at the myogenin promoter. These data strongly suggest that in addition to its widely accepted role as an activator of differentiation-specific genes, MyoD also can perform as a transcriptional repressor in proliferating myoblasts while in partnership with a HDAC.
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Developmental Biology, 2004
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Skeletal Muscle
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The SWI/SNF Subunit/Tumor Suppressor BAF47/INI1 Is Essential in Cell Cycle Arrest upon Skeletal Muscle Terminal Differentiation
PLoS ONE, 2014
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Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex
Genes & Development, 2008
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BioArchitecture, 2012
Contrasting roles for MyoD in organizing myogenic promoter structures during embryonic skeletal muscle development
Developmental Dynamics, 2014
Background: Among the complexities of skeletal muscle differentiation is a temporal distinction in the onset of expression of different lineage‐specific genes. The lineage‐determining factor MyoD is bound to myogenic genes at the onset of differentiation whether gene activation is immediate or delayed. How temporal regulation of differentiation‐specific genes is established remains unclear. Results: Using embryonic tissue, we addressed the molecular differences in the organization of the myogenin and muscle creatine kinase (MCK) gene promoters by examining regulatory factor binding as a function of both time and spatial organization during somitogenesis. At the myogenin promoter, binding of the homeodomain factor Pbx1 coincided with H3 hyperacetylation and was followed by binding of co‐activators that modulate chromatin structure. MyoD and myogenin binding occurred subsequently, demonstrating that Pbx1 facilitates chromatin remodeling and modification before myogenic regulatory fact...
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Nucleic Acids Research, 2021
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The EMBO Journal, 2010
The chromatin-remodelling complex SNF2-related CBP activator protein (SRCAP) regulates chromatin structure in yeast by modulating the exchange of histone H2A for the H2A.Z variant. Here, we have investigated the contribution of H2A.Z-mediated chromatin remodelling to mammalian cell differentiation reprogramming. We show that the SRCAP subunit named ZNHIT1 or p18 Hamlet , which is a substrate of p38 MAPK, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 MAPK-dependent manner. We also show that p18 Hamlet is required for H2A.Z accumulation into this genomic region and for subsequent muscle gene transcriptional activation. Accordingly, downregulation of several subunits or the SRCAP complex impairs muscle gene expression. These results identify SRCAP/H2A.Z-mediated chromatin remodelling as a key early event in muscle differentiation-specific gene expression. We also propose a mechanism by which p38 MAPK-mediated signals are converted into chromatin structural changes, thereby facilitating transcriptional activation during mammalian cell differentiation.
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PLoS ONE, 2010
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HDAC-regulated myomiRs control BAF60 variant exchange and direct the functional phenotype of fibro-adipogenic progenitors in dystrophic muscles
Genes & Development, 2014
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