Two domains of MyoD mediate transcriptional activation of genes in repressive chromatin: a mechanism for lineage determination in myogenesis.

Gerber, Anthony N.; Klesert, Todd R.; Bergstrom, Donald A.; Tapscott, Stephen J.

doi:10.1101/gad.11.4.436

Cited by 254 publications

(223 citation statements)

References 75 publications

(80 reference statements)

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“…The importance of the acetyltransferases p300 and PCAF in the myogenic program is underscored by experiments of either functional or genetic inactivation of p300 or PCAF, which is sufficient to block skeletal myogenesis in cultured cells and in mouse embryos (Puri et al, 1997b;Polesskaya et al, 2001b;Roth et al, 2003). According to their early pattern of expression in muscle progenitors, MyoD and Myf5 have the unique ability to initiate the myogenic program by promoting chromatin remodelling at previously silent loci (Gerber et al, 1997). This ability is conferred by two conserved regions, a cystein-histidine rich region and the carboxy-terminal region.…”

Section: Stages 3 and 4-activation And Maintainance Of The Differentimentioning

confidence: 99%

The epigenetic network regulating muscle development and regeneration

Palacios

Puri

2005

Journal Cellular Physiology

104

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This review focuses on our current knowledge of the epigenetic changes regulating gene expression at the chromatin and DNA level, independently on the primary DNA sequence, to reprogram the nuclei of muscle precursors during developmental myogenesis and muscle regeneration. These epigenetic marks provide the blueprint by which the extra-cellular cues are interpreted at the nuclear level by the transcription machinery to select the repertoire of tissue-specific genes to be expressed. The reversibility of some of these changes necessarily reflects the dynamic nature of skeletal myogenesis, which entails the progression through two antagonistic processes-proliferation and differentiation. Other epigenetic modifications are instead associated to events conventionally considered as irreversible-e.g. maintenance of lineage commitment and terminal differentiation. However, recent results support the possibility that these events can be reversed, at least upon certain experimental conditions, thereby revealing a dynamic nature of many of the epigenetic modifications underlying skeletal myogenesis. The elucidation of the epigenetic network that regulates transcription during developmental myogenesis and muscle regeneration might provide the information instrumental to devise pharmacological interventions toward selective manipulation of gene expression to promote regeneration of skeletal muscles and possibly other tissue.

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Section: Stages 3 and 4-activation And Maintainance Of The Differentimentioning

confidence: 99%

The epigenetic network regulating muscle development and regeneration

Palacios

Puri

2005

Journal Cellular Physiology

104

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“…But this function of myogenin is in complete contrast to the functions of Myf5, MyoD, and MRF4, none of which is needed for formation of skeletal muscle in mice (9). Another model was recently proposed on the basis of structural differences between the MyoD and myogenin proteins (14), according to previous studies that emphasized the abilities of determination factors to remodel the chromatin at the promoter of silent muscle genes (48). In this model, the determination factors initiate the expression of an array of genes that are subsequently enhanced and maintained in transcription by the differentiation factors, permitting the full level of gene expression needed for terminal differentiation.…”

Section: Restricted Expression Of Myogenin In Oxidative Myofibers Of mentioning

confidence: 99%

Two Myogenin-related Genes Are Differentially Expressed inXenopus laevis Myogenesis and Differ in Their Ability to Transactivate Muscle Structural Genes

Charbonnier

Gaspera

Armand

et al. 2002

Journal of Biological Chemistry

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Among the myogenic regulatory factors, myogenin is a transcriptional activator situated at a crucial position for terminal differentiation in muscle development. It is unclear at present whether myogenin exhibits unique specificities to transactivate late muscular markers. During Xenopus development, the accumulation of myogenin mRNA is restricted to secondary myogenesis, at the onset of the appearance of adult isoforms of ␤-tropomyosin and myosin heavy chain. To determine the role of myogenin in the isoform switch of these contractile proteins, we characterized and directly compared the functional properties of myogenin with other myogenic regulatory factors in Xenopus embryos. Two distinct cDNAs related to myogenin, XmyogU1 and XmyogU2, were differentially expressed during myogenesis and in adult tissues, in which they preferentially accumulated in oxidative myofibers. Animal cap assays in Xenopus embryos revealed that myogenin, but not the other myogenic regulatory factors, induced expression of embryonic/larval isoforms of the ␤-tropomyosin and myosin heavy chain genes. Only XmyogU1 induced expression of the adult fast isoform of the myosin heavy chain gene. This is the first demonstration of a specific transactivation of one set of muscle structural genes by myogenin.The members of the MyoD gene family, including myoD (1), myogenin (2), myf5 (3), and MRF4 (4, 5), encode myogenic transcription factors (MRFs) 1 able to convert non-muscle cells to a muscle phenotype in culture (6, 7). First identified in mammals, all four proteins share a highly conserved central region related to the basic helix-loop-helix domain of the c-Myc superfamily. The MRFs are specifically expressed in skeletal muscle, with non-identical patterns of expression (8), and form a regulatory network controlling muscle determination and/or differentiation. Experiments using various MRF knockout mice have progressively elucidated the hierarchical relationships among the MRFs and established that functional redundancy is a feature of the MRF regulatory network. Thus, MyoD and Myf5 play overlapping roles in myoblast specification, whereas myogenin and either MyoD or MRF4 are required for differentiation (9). However, the redundant functions of MyoD and MRF4 appear not to overlap with those of myogenin (10). Knockout mice lacking the myogenin gene die at birth due to severe muscle deficiency, despite normal levels of MyoD and Myf5 (11,12). Recent studies have shown that the role of myogenin in muscle formation is distinct from that of MyoD and that this difference is due to functional specialization, and not just regulation of expression (13,14).Surprisingly little is known about the identity of muscle genes that are selectively activated by myogenin and that cannot be activated by the other myogenic regulators. Indeed, all the MRFs can transactivate muscle-specific gene expression by interacting with the consensus nucleotide motif, CANNTG, also called the E box, and they are all believed to bind to their target sequences as heterodimers with ...

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“…MRF competence to promote transcription of muscle genes relies on the interaction with the SWI/SNF chromatinremodeling complex [4,5]. SWI/SNF complex appears to mediate the unique ability of MyoD and Myf5 to remodel the chromatin and activate transcription at previously silent muscle loci [6,7], but is also required for the maintenance of muscle gene expression at later stages of skeletal myogenesis [8]. SWI/SNF complexes are composed of two mutually exclusive enzymatic subunits (the ATPases Brahma (Brm) and Brm-related gene 1 (Brg1)) and a number of structural subunits, collectively referred to as Brg1/Brm-associated factors (BAFs) [9,10].…”

Section: Introductionmentioning

confidence: 99%

Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis

et al. 2015

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Although the two catalytic subunits of the SWI/SNF chromatinremodeling complex-Brahma (Brm) and Brg1-are almost invariably co-expressed, their mutually exclusive incorporation into distinct SWI/SNF complexes predicts that Brg1-and Brm-based SWI/SNF complexes execute specific functions. Here, we show that Brg1 and Brm have distinct functions at discrete stages of muscle differentiation. While Brg1 is required for the activation of muscle gene transcription at early stages of differentiation, Brm is required for Ccnd1 repression and cell cycle arrest prior to the activation of muscle genes. Ccnd1 knockdown rescues the ability to exit the cell cycle in Brm-deficient myoblasts, but does not recover terminal differentiation, revealing a previously unrecognized role of Brm in the activation of late muscle gene expression independent from the control of cell cycle. Consistently, Brm null mice displayed impaired muscle regeneration after injury, with aberrant proliferation of satellite cells and delayed formation of new myofibers. These data reveal stage-specific roles of Brm during skeletal myogenesis, via formation of repressive and activatory SWI/SNF complexes.

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Two domains of MyoD mediate transcriptional activation of genes in repressive chromatin: a mechanism for lineage determination in myogenesis.

Cited by 254 publications

References 75 publications

The epigenetic network regulating muscle development and regeneration

The epigenetic network regulating muscle development and regeneration

Two Myogenin-related Genes Are Differentially Expressed inXenopus laevis Myogenesis and Differ in Their Ability to Transactivate Muscle Structural Genes

Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis

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