A MyoD -generated feed-forward circuit temporally patterns gene expression dining skeletal muscle differentiation

Bennett Penn, Donald A. Bergstrom, F. Jeffrey Dilworth, Eyal Bengal, Stephen J. Tapscott

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

The development and differentiation of distinct cell types is achieved through the sequential expression of subsets of genes; yet, the molecular mechanisms that temporally pattern gene expression remain largely unknown. In skeletal myogenesis, gene expression is initiated by MyoD and includes the expression of specific Mef2 isoforms and activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Here, we show that p38 activity facilitates MyoD and Mef2 binding at a subset of late-activated promoters, and the binding of Mef2D recruits Pol II. Most importantly, expression of late-activated genes can be shifted to the early stages of differentiation by precocious activation of p38 and expression of Mef2D, demonstrating that a MyoD-mediated feed-forward circuit temporally patterns gene expression.

Original languageEnglish (US)
Pages (from-to)2348-2353
Number of pages6
JournalGenes and Development
Volume18
Issue number19
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

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Keywords

  • Feed-forward
  • MAP kinase
  • Mef2
  • MyoD
  • p38
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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