The circuitry of a master switch: Myod and the regulation of skeletal muscle gene transcription

Tapscott, Stephen J.

doi:10.1242/dev.01874

Cited by 646 publications

(629 citation statements)

References 103 publications

(118 reference statements)

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“…Interestingly, genes associated to MyoD peaks unique to proliferating myoblasts were the only group that did not exhibit an overall increase in expression during early differentiation. Taken together, our analyses revealed a residue-specific histone acetylation associated with MyoD, which acts as a master regulator to establish myogenic transcription program pertinent to early differentiation [41,42]. …”

Section: Resultsmentioning

confidence: 99%

Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation

et al. 2018

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Molecular regulation of stem cell differentiation is exerted through both genetic and epigenetic determinants over distal regulatory or enhancer regions. Understanding the mechanistic action of active or poised enhancers is therefore imperative for control of stem cell differentiation. Based on the genome-wide co-occurrence of different epigenetic marks in committed proliferating myoblasts, we have previously generated a 14-state chromatin state model to profile rexinoid-responsive histone acetylation in early myoblast differentiation. Here, we delineate the functional mode of transcription regulators during early myogenic differentiation using genome-wide chromatin state association. We define a role of transcriptional coactivator p300, when recruited by muscle master regulator MyoD, in the establishment and regulation of myogenic loci at the onset of myoblast differentiation. In addition, we reveal an enrichment of loci-specific histone acetylation at p300 associated active or poised enhancers, particularly when enlisted by MyoD. We provide novel molecular insights into the regulation of myogenic enhancers by p300 in concert with MyoD. Our studies present a valuable aptitude for driving condition-specific chromatin state or enhancers pharmacologically to treat muscle-related diseases and for the identification of additional myogenic targets and molecular interactions for therapeutic development.Abbreviations: MRF: Muscle regulatory factor; HAT: Histone acetyltransferase; CBP: CREB-binding protein; ES: Embryonic stem; ATCC: American type culture collection; DM: Differentiation medium; DMEM: Dulbecco’s Modified Eagle Medium; GM: Growth medium; GO: Gene ontology; GREAT: Genomic regions enrichment of annotations tool; FPKM: Fragments per kilobase of transcript per million; GEO: Gene expression omnibus; MACS: Model-based analysis for ChIP-seq

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Section: Resultsmentioning

confidence: 99%

Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation

et al. 2018

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“…MRFs consist of MyoD, Myf5, MRF4, and myogenin, all being members of the basic helix-loop-helix (bHLH) family of proteins [4][5][6], while MEF2s consist of MEF2A, MEF2B, MEF2C, and MEF2D that belong to the MADS box family of proteins [7,8]. MRFs preferentially pair with the ubiquitously expressed E proteins (e.g., E12/E47) that also belong to the bHLH family, in order to efficiently bind to a consensus site (i.e., CANNTG, also called an E box) in the regulatory regions of many muscle-specific genes [9,10].…”

Section: Introductionmentioning

confidence: 99%

Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration

Xiao

Wang

et al. 2010

Cell Res

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Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays important roles during inflammation. However, its roles in myoblast differentiation and muscle regeneration remain unexplored. We show here that OSM potently inhibited myoblast differentiation mainly by activating the JAK1/STAT1/STAT3 pathway. OSM downregulated myocyte enhancer-binding factor 2A (MEF2A), upregulated the expression of Id1 and Id2, and inhibited the transcriptional activity of MyoD and MEF2. In addition, OSM also enhanced the expression of STAT3 and OSM receptor, which constituted a positive feedback loop to further amplify OSM-induced signaling. Moreover, we found that STAT1 physically associated with MEF2 and repressed its transcriptional activity, which could account for the OSM-mediated repression of MEF2. Although undetectable in normal muscles in vivo, OSM was rapidly induced on muscle injury and then promptly downregulated just before the majority of myoblasts differentiate. Prolonged expression of OSM in muscles compromised the regeneration process without affecting myoblast proliferation, suggesting that OSM functions to prevent proliferating myoblasts from premature differentiation during the early phase of muscle regeneration.

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“…During regeneration, skeletal muscle must strike a delicate balance between differentiation and self-renewal to maintain SC homeostasis 9 . This process is tightly regulated by extrinsic cues, namely by various factors in the stem-cell niche and by intrinsic transcriptional regulators, including Pax7, Myf5 and MyoD 4,6,[10][11][12] . Pax7 contributes to SC activation, proliferation, self-renewal and differentiation by regulating expression of its target genes, such as Myf5 and MyoD 13,14 .…”

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confidence: 99%

MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice

Zhai

et al. 2015

Nat Commun

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Skeletal muscle stem cells, called satellite cells, are a quiescent heterogeneous population. Their heterogeneity is influenced by Pax7, a well-defined transcriptional regulator of satellite cell functions that defines two subpopulations: Pax7 Hi and Pax7 Lo . However, the mechanisms by which these subpopulations are established and maintained during myogenesis are not completely understood. Here we show that miR-431, which is predominantly expressed in the skeletal muscle, mediates satellite cell heterogeneity by fine-tuning Pax7 levels during muscle development and regeneration. In miR-431 transgenic mice, the Pax7 Lo subpopulation is enriched, enhances myogenic differentiation and accelerates muscle regeneration. Notably, miR-431 attenuates the muscular dystrophic phenotype in mdx mice and may be a potential therapeutic target in muscular diseases. miR-431 transgenic mice are a unique genetic model for investigating the cellular features and biological functions of Pax7 Lo satellite cells during muscle development and regeneration.

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The circuitry of a master switch: Myod and the regulation of skeletal muscle gene transcription

Cited by 646 publications

References 103 publications

Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation

Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation

Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration

MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice

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