Regulation of cyclin D2 gene expression by the Myc/Max/Mad network: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter

  1. Caroline Bouchard1,4,
  2. Oliver Dittrich2,4,
  3. Astrid Kiermaier1,4,
  4. Karen Dohmann2,
  5. Annette Menkel2,
  6. Martin Eilers1, and
  7. Bernhard Lüscher2,3,5
  1. 1Institute for Molecular Biology and Tumor Research, 35033 Marburg, Germany; 2Institute for Molecular Biology, Medizinische Hochschule Hannover, 30625 Hannover, Germany; 3Laboratory of Biochemistry and Molecular Biology, Institute of Biochemistry, RWTH, 52057 Aachen, Germany

Abstract

Myc oncoproteins promote cell cycle progression in part through the transcriptional up-regulation of the cyclin D2 gene. We now show that Myc is bound to the cyclin D2 promoter in vivo. Binding of Myc induces cyclin D2 expression and histone acetylation at a single nucleosome in a MycBoxII/TRRAP-dependent manner. Down-regulation of cyclin D2 mRNA expression in differentiating HL60 cells is preceded by a switch of promoter occupancy from Myc/Max to Mad/Max complexes, loss of TRRAP binding, increased HDAC1 binding, and histone deacetylation. Thus, recruitment of TRRAP and regulation of histone acetylation are critical for transcriptional activation by Myc.

Keywords

Footnotes

  • 4 These authors contributed equally to this work.

  • 5 Corresponding author.

  • E-MAIL luescher{at}ruth-aachen.de; FAX 49-241-8888427.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.907901.

    • Received April 30, 2001.
    • Accepted June 21, 2001.
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