Mechanism of polymerase II transcription repression by the histone variant macroH2A

Cécile Marie Doyen, Woojin An, Dimitar Angelov, Vladimir Bondarenko, Flore Mietton, Vassily M. Studitsky, Ali Hamiche, Robert G. Roeder, Philippe Bouvet, Stefan Dimitrov

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macroH2A (mH2A) is an unusual histone variant consisting of a histone H2A-like domain fused to a large nonhistone region. In this work, we show that histone mH2A represses p300- and Gal4-VP16-dependent polymerase II transcription, and we have dissected the mechanism by which this repression is realized. The repressive effect of mH2A is observed at the level of initiation but not at elongation of transcription, and mH2A interferes with p300-dependent histone acetylation. The nonhistone region of mH2A is responsible for both the repression off initiation of transcription and the inhibition of histone acetylation. In addition, the presence of this domain of mH2A within the nucleosome is able to block nucleosome remodeling and sliding of the histone octamer to neighboring BNA segments by the remodelers SWI/SNF and ACF. These data unambiguously identify mH2A as a strong transcriptional represser and show that the repressive effect of mH2A is realized on at least two different transcription activation chromatin-dependent pathways: histone acetylation and nucleosome remodeling.

Original languageEnglish
Pages (from-to)1156-1164
Number of pages9
JournalMolecular and Cellular Biology
Issue number3
Publication statusPublished - Feb 2006
Externally publishedYes


ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Doyen, C. M., An, W., Angelov, D., Bondarenko, V., Mietton, F., Studitsky, V. M., Hamiche, A., Roeder, R. G., Bouvet, P., & Dimitrov, S. (2006). Mechanism of polymerase II transcription repression by the histone variant macroH2A. Molecular and Cellular Biology, 26(3), 1156-1164.