Authors:
EM Nascimento, CL Cox, S MacArthur, S Hussain, M Trotter, S Blanco, M Suraj, J Nichols, B Kübler, SA Benitah, B Hendrich, DT Odom, M Frye
Journal name: 
Nat Cell Biol
Citation info: 
13(12):1395-1405
Abstract: 
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.
DOI: 
http://doi.org/10.1038/ncb2385
Research group: 
Odom Group
E-pub date: 
20 Nov 2011