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Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6205-10. doi: 10.1073/pnas.1019644108. Epub 2011 Mar 28.

Drosophila histone H2A variant (H2Av) controls poly(ADP-ribose) polymerase 1 (PARP1) activation in chromatin.

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1
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

Abstract

According to the histone code hypothesis, histone variants and modified histones provide binding sites for proteins that change the chromatin state to either active or repressed. Here, we identify histone variants that regulate the targeting and enzymatic activity of poly(ADP-ribose) polymerase 1 (PARP1), a chromatin regulator in higher eukaryotes. We demonstrate that PARP1 is targeted to chromatin by association with the histone H2A variant (H2Av)--the Drosophila homolog of the mammalian histone H2A variants H2Az/H2Ax--and that subsequent phosphorylation of H2Av leads to PARP1 activation. This two-step mechanism of PARP1 activation controls transcription at specific loci in a signal-dependent manner. Our study establishes the mechanism through which histone variants and changes in the histone modification code control chromatin-directed PARP1 activity and the transcriptional activation of target genes.

PMID:
21444826
PMCID:
PMC3076809
DOI:
10.1073/pnas.1019644108
[Indexed for MEDLINE]
Free PMC Article
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