Myc influences global chromatin structure

Paul S Knoepfler, Xiao Yong Zhang, Pei Feng Cheng, Philip R. Gafken, Steven B. McMahon, Robert N. Eisenman

Research output: Contribution to journalArticle

288 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2723-2734
Number of pages12
JournalEMBO Journal
Volume25
Issue number12
DOIs
StatePublished - Jun 21 2006
Externally publishedYes

Fingerprint

Chromatin
Histone Code
myc Genes
Methylation
Proto-Oncogenes
Oncogene Proteins
Cell proliferation
Cell growth
Histones
Condensation
Carcinogenesis
Proteins
Transcription Factors
Up-Regulation
Stem Cells
Genes
Maintenance
Cell Proliferation
Growth
Neoplasms

Keywords

  • Chromatin
  • Epigenetics
  • Histone modification
  • Myc
  • Stem and progenitor cells

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Knoepfler, P. S., Zhang, X. Y., Cheng, P. F., Gafken, P. R., McMahon, S. B., & Eisenman, R. N. (2006). Myc influences global chromatin structure. EMBO Journal, 25(12), 2723-2734. https://doi.org/10.1038/sj.emboj.7601152

Myc influences global chromatin structure. / Knoepfler, Paul S; Zhang, Xiao Yong; Cheng, Pei Feng; Gafken, Philip R.; McMahon, Steven B.; Eisenman, Robert N.

In: EMBO Journal, Vol. 25, No. 12, 21.06.2006, p. 2723-2734.

Research output: Contribution to journalArticle

Knoepfler, PS, Zhang, XY, Cheng, PF, Gafken, PR, McMahon, SB & Eisenman, RN 2006, 'Myc influences global chromatin structure', EMBO Journal, vol. 25, no. 12, pp. 2723-2734. https://doi.org/10.1038/sj.emboj.7601152
Knoepfler PS, Zhang XY, Cheng PF, Gafken PR, McMahon SB, Eisenman RN. Myc influences global chromatin structure. EMBO Journal. 2006 Jun 21;25(12):2723-2734. https://doi.org/10.1038/sj.emboj.7601152
Knoepfler, Paul S ; Zhang, Xiao Yong ; Cheng, Pei Feng ; Gafken, Philip R. ; McMahon, Steven B. ; Eisenman, Robert N. / Myc influences global chromatin structure. In: EMBO Journal. 2006 ; Vol. 25, No. 12. pp. 2723-2734.
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