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  • The EMBO Journal (2006) 25, 2723 - 2734
  • doi:10.1038/sj.emboj.7601152

Published online: 25 May 2006

Myc influences global chromatin structure

Paul S Knoepfler1, Xiao-yong Zhang2, Pei Feng Cheng1, Philip R Gafken3, Steven B McMahon2 and Robert N Eisenman1

  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  2. The Wistar Institute, Gene Expression and Regulation Program, Philadelphia, PA, USA
  3. Proteomics Facility, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Correspondence to:

Robert N Eisenman, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109-4417, USA. Tel.: +1 206 667 4445; Fax: +1 206 667 6522; E-mail: eisenman@fhcrc.org

Received 6 December 2005; Accepted 27 April 2006

The family of myc proto-oncogenes encodes transcription factors (c-, N-, and L-Myc) that regulate cell growth and proliferation and are involved in the etiology of diverse cancers. Myc proteins are thought to function by binding and regulating specific target genes. Here we report that Myc proteins are required for the widespread maintenance of active chromatin. Disruption of N-myc in neuronal progenitors and other cell types leads to nuclear condensation accompanied by large-scale changes in histone modifications associated with chromatin inactivation, including hypoacetylation and altered methylation. These effects are largely reversed by exogenous Myc as well as by differentiation and are mimicked by the Myc antagonist Mad1. The first chromatin changes are evident within 6 h of Myc loss and lead to changes in chromatin structure. Myc widely influences chromatin in part through upregulation of the histone acetyltransferase GCN5. This study provides the first evidence for regulation of global chromatin structure by an oncoprotein and may explain the broad effects of Myc on cell behavior and tumorigenesis.

  • Keywords:

    • chromatin,
    • epigenetics,
    • histone modification,
    • Myc,
    • stem and progenitor cells