The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity.
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.
Ouararhni
Khalid
K
Laboratoire Epigénétique et Cancer, Centre National de la Recherche Scientifique FRE 2944, 94801 Villejuif, France.
Hadj-Slimane
Réda
R
Ait-Si-Ali
Slimane
S
Robin
Philippe
P
Mietton
Flore
F
Harel-Bellan
Annick
A
Dimitrov
Stefan
S
Hamiche
Ali
A
D002843:Chromatin / Q000235:genetics / Q000502:physiology; D003001:Cloning, Molecular; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic; D014644:Genetic Variation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000502:physiology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic
D002843:Chromatin; D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C091879:HSPA2 protein, human; D006657:Histones; D009707:Nucleosomes; D034741:RNA, Small Interfering; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases