E2f3b plays an essential role in myogenic differentiation through isoform-specific gene regulation

Patrik Asp, Diego Acosta-Alvear, Mary Tsikitis, Chris Van Oevelen, Brian David Dynlacht

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Current models posit that E2F transcription factors can be divided into members that either activate or repress transcription, in part through collaboration with the retinoblastoma (pRb) tumor suppressor family. The E2f3 locus encodes E2f3a and E2f3b proteins, and available data suggest that they regulate cell cycle-dependent gene expression through opposing transcriptional activating and repressing activities in growing and quiescent cells, respectively. However, the role, if any, of E2F proteins, and in particular E2f3, in myogenic differentiation is not well understood. Here, we dissect the contributions of E2f3 isoforms and other activating and repressing E2Fs to cell cycle exit and differentiation by performing genome-wide identification of isoform-specific targets. We show that E2f3a and E2f3b target genes are involved in cell growth, lipid metabolism, and differentiation in an isoform-specific manner. Remarkably, using gene silencing, we show that E2f3b, but not E2f3a or other E2F family members, is required for myogenic differentiation, and that this requirement for E2f3b does not depend on pRb. Our functional studies indicate that E2f3b specifically attenuates expression of genes required to promote differentiation. These data suggest how diverse E2F isoforms encoded by a single locus can play opposing roles in cell cycle exit and differentiation.

Original languageEnglish (US)
Pages (from-to)37-53
Number of pages17
JournalGenes and Development
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2009

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Keywords

  • Cell cycle
  • ChIP-on-chip
  • E2F
  • E2f3b
  • Myogenic differentiation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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