Mechanism of Polymerase II Transcription Repression by the Histone Variant macroH2A

Institut Albert Bonniot, INSERM U309, 38706 La Tronche cedex, France.
Molecular and Cellular Biology (Impact Factor: 4.78). 03/2006; 26(3):1156-64. DOI: 10.1128/MCB.26.3.1156-1164.2006
Source: PubMed


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 of 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 DNA segments by the remodelers SWI/SNF and ACF. These data unambiguously identify mH2A as a strong
transcriptional repressor 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.

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Available from: Dimitar Angelov
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    • "The name mH2A is derived from the structural feature of this histone variant, which contains a large nonhistone region (NHR), known as the macro domain, on its N-terminus.41 As a consequence, the NHR of mH2A alters nucleosome structure and interferes with the transcription machinery.42 "
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    • "The repressive mode of action for the macrohistones has been attributed to the interference with p300-dependent histone acetylation and the hindrance of transcription factor NF-κβ binding, as well as the inhibition of nucleosome remodeling and repositioning by SWI/SNF and ACF [18], [19]. The later finding has recently been challenged by data showing that mH2A1-containing nucleosomes were efficiently mobilized by both complexes, although mH2A1 specifically reduced SWI/SNF recruitment to a DNA template containing a nucleosome positioning sequence [20]. "
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    • "The chromatin-remodelling complex SWI/SNF is unable to remodel in the presence of macroH2A. MacroH2A also represses RNA polymerase II transcription (Doyen et al. 2006). In agreement with this, macroH2A is depleted from active genes (Changolkar and Pehrson 2006). "
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