| First Author | Soleimani VD | Year | 2012 |
| Journal | Mol Cell | Volume | 47 |
| Issue | 3 | Pages | 457-68 |
| PubMed ID | 22771117 | Mgi Jnum | J:188049 |
| Mgi Id | MGI:5439050 | Doi | 10.1016/j.molcel.2012.05.046 |
| Citation | Soleimani VD, et al. (2012) Snail regulates MyoD binding-site occupancy to direct enhancer switching and differentiation-specific transcription in myogenesis. Mol Cell 47(3):457-68 |
| abstractText | In skeletal myogenesis, the transcription factor MyoD activates distinct transcriptional programs in progenitors compared to terminally differentiated cells. Using ChIP-Seq and gene expression analyses, we show that in primary myoblasts, Snail-HDAC1/2 repressive complex binds and excludes MyoD from its targets. Notably, Snail binds E box motifs that are G/C rich in their central dinucleotides, and such sites are almost exclusively associated with genes expressed during differentiation. By contrast, Snail does not bind the A/T-rich E boxes associated with MyoD targets in myoblasts. Thus, Snai1-HDAC1/2 prevent MyoD occupancy on differentiation-specific regulatory elements, and the change from Snail to MyoD binding often results in enhancer switching during differentiation. Furthermore, we show that a regulatory network involving myogenic regulatory factors (MRFs), Snai1/2, miR-30a, and miR-206 acts as a molecular switch that controls entry into myogenic differentiation. Together, these results reveal a regulatory paradigm that directs distinct gene expression programs in progenitors versus terminally differentiated cells. |
