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The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity.

Abstract : The histone variant mH2A is believed to be involved in transcriptional repression, but how it exerts its function remains elusive. By using chromatin immunoprecipitation and tandem affinity immunopurification of the mH2A1.1 nucleosome complex, we identified numerous genes with promoters containing mH2A1.1 nucleosomes. In particular, the promoters of the inducible Hsp70.1 and Hsp70.2 genes, but not that of the constitutively expressed Hsp70.8, were highly enriched in mH2A1.1. PARP-1 was identified as a part of the mH2A1.1 nucleosome complex and was found to be associated with the Hsp70.1 promoter. A specific interaction between mH2A1.1 and PARP-1 was demonstrated and found to be associated with inactivation of PARP-1 enzymatic activity. Heat shock released both mH2A1.1 and PARP-1 from the Hsp70.1 promoter and activated PARP-1 automodification activity. The data we present point to a novel mechanism for control of Hsp70.1 gene transcription. mH2A1.1 recruits PARP-1 to the promoter, thereby inactivating it. Upon heat shock, the Hsp70.1 promoter-bound PARP-1 is released to activate transcription through ADP-ribosylation of other Hsp70.1 promoter-bound proteins.
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Contributor : Annick Harel-Bellan Connect in order to contact the contributor
Submitted on : Tuesday, October 10, 2006 - 1:05:44 PM
Last modification on : Wednesday, December 2, 2020 - 5:48:05 PM

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Khalid Ouararhni, Réda Hadj-Slimane, Slimane Ait-Si-Ali, Philippe Robin, Flore Mietton, et al.. The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity.. Genes and Development, Cold Spring Harbor Laboratory Press, 2006, 20 (23), pp.3324-36. ⟨10.1101/gad.396106⟩. ⟨inserm-00105117⟩



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