| First Author | Nascimento EM | Year | 2011 |
| Journal | Nat Cell Biol | Volume | 13 |
| Issue | 12 | Pages | 1395-405 |
| PubMed ID | 22101514 | Mgi Jnum | J:178941 |
| Mgi Id | MGI:5300654 | Doi | 10.1038/ncb2385 |
| Citation | Nascimento EM, et al. (2011) The opposing transcriptional functions of Sin3a and c-Myc are required to maintain tissue homeostasis. Nat Cell Biol 13(12):1395-405 |
| abstractText | How the proto-oncogene c-Myc balances the processes of stem-cell self-renewal, proliferation and differentiation in adult tissues is largely unknown. We explored c-Myc's transcriptional roles at the epidermal differentiation complex, a locus essential for skin maturation. Binding of c-Myc can simultaneously recruit (Klf4, Ovol-1) and displace (Cebpa, Mxi1 and Sin3a) specific sets of differentiation-specific transcriptional regulators to epidermal differentiation complex genes. We found that Sin3a causes deacetylation of c-Myc protein to directly repress c-Myc activity. In the absence of Sin3a, genomic recruitment of c-Myc to the epidermal differentiation complex is enhanced, and re-activation of c-Myc-target genes drives aberrant epidermal proliferation and differentiation. Simultaneous deletion of c-Myc and Sin3a reverts the skin phenotype to normal. Our results identify how the balance of two transcriptional key regulators can maintain tissue homeostasis through a negative feedback loop. |
