Snail Regulates MyoD Binding-site Occupancy to Direct Enhancer Switching and Differentiation-specific Transcription in Myogenesis

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Jul 10

PMID 22771117

Citations 111

Authors

Vahab D Soleimani

Hang Yin

Arezu Jahani-Asl

Hong Ming

Christel E M Kockx

Wilfred F J van IJcken

Frank Grosveld

Michael A Rudnicki

Affiliations

Soon will be listed here.

Abstract

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.

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