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Development June 1, 2012; 139 (11): 1910-20.
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Sim2 prevents entry into the myogenic program by repressing MyoD transcription during limb embryonic myogenesis.

Havis E , Coumailleau P , Bonnet A , Bismuth K , Bonnin MA , Johnson R , Fan CM , Relaix F , Shi DL , Duprez D .

The basic helix-loop-helix transcription factor MyoD is a central actor that triggers the skeletal myogenic program. Cell-autonomous and non-cell-autonomous regulatory pathways must tightly control MyoD expression to ensure correct initiation of the muscle program at different places in the embryo and at different developmental times. In the present study, we have addressed the involvement of Sim2 (single-minded 2) in limb embryonic myogenesis. Sim2 is a bHLH-PAS transcription factor that inhibits transcription by active repression and displays enhanced expression in ventral limb muscle masses during chick and mouse embryonic myogenesis. We have demonstrated that Sim2 is expressed in muscle progenitors that have not entered the myogenic program, in different experimental conditions. MyoD expression is transiently upregulated in limb muscle masses of Sim2(-/-) mice. Conversely, Sim2 gain-of-function experiments in chick and Xenopus embryos showed that Sim2 represses MyoD expression. In addition, we show that Sim2 represses the activity of the mouse MyoD promoter in primary myoblasts and is recruited to the MyoD core enhancer in embryonic mouse limbs. Sim2 expression is non-autonomously and negatively regulated by the dorsalising factor Lmx1b. We propose that Sim2 represses MyoD transcription in limb muscle masses, through Sim2 recruitment to the MyoD core enhancer, in order to prevent premature entry into the myogenic program. This MyoD repression is predominant in ventral limb regions and is likely to contribute to the differential increase of the global mass of ventral muscles versus dorsal muscles.

PubMed ID: 22513369
PMC ID: PMC3347684
Article link: Development
Grant support: [+]

Species referenced: Xenopus
Genes referenced: dll1 gal.2 hprt1 lmx1b.1 lmx1b.2 myf5 myod1 notch1 pax3 pax7 pitx2 sim2 six1 six4 tcf3

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References [+] :
Aleman, Inhibition of Single Minded 2 gene expression mediates tumor-selective apoptosis and differentiation in human colon cancer cells. 2005, Pubmed