Binding of c-Myc to chromatin mediates mitogen-induced acetylation of histone H4 and gene activation

S. R. Frank, M. Schroeder, P. Fernandez, S. Taubert, B. Amati

Research output: Contribution to journalArticlepeer-review

Abstract

The Myc protein binds DNA and activates transcription by mechanisms that are still unclear. We used chromatin immunoprecipitation (ChIP) to evaluate Myc-dependent changes in histone acetylation at seven target loci. Upon serum stimulation of Rat1 fibroblasts, Myc associated with chromatin, histone H4 became locally hyperacetylated, and gene expression was induced. These responses were lost or severely impaired in Myc-deficient cells, but were restored by adenoviral delivery of Myc simultaneous with mitogenic stimulation. When targeted to chromatin in the absence of mitogens, Myc directly induced H4 acetylation. In addition, Myc recruited TRRAP to chromatin, consistent with a role for this cofactor in histone acetylation. Finally, unlike serum, Myc alone was very inefficient in inducing expression of most target genes. Myc therefore governs a step, most likely H4 acetylation, that is required but not sufficient for transcriptional activation. We propose that Myc acts as a permissive factor, allowing additional signals to activate target promoters.

Original languageEnglish
Pages (from-to)2069-2082
Number of pages14
JournalGenes and Development
Volume15
Issue number16
DOIs
Publication statusPublished - Aug 15 2001

Keywords

  • Chromatin
  • HAT
  • Histone acetylation
  • Myc
  • Nucleolin
  • TRRAP

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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