The Opposing Transcriptional Functions of Sin3a and C-Myc Are Required to Maintain Tissue Homeostasis

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2011 Nov 22

PMID 22101514

Citations 42

Authors

Elisabete M Nascimento

Claire L Cox

Stewart MacArthur

Shobbir Hussain

Matthew Trotter

Sandra Blanco

Menon Suraj

Jennifer Nichols

Bernd Kubler

Salvador Aznar Benitah

Brian Hendrich

Duncan T Odom

Michaela Frye

Affiliations

Soon will be listed here.

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.

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