DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during transcription.
Fiche publication
Date publication
septembre 2019
Journal
Nature chemical biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr COIN Frédéric, Dr EGLY Jean-Marc, Dr LE MAY Nicolas
Tous les auteurs :
Semer M, Bidon B, Larnicol A, Caliskan G, Catez P, Egly JM, Coin F, Le May N
Lien Pubmed
Résumé
Post-translational modifications of histone variant H2A.Z accompany gene transactivation, but its modifying enzymes still remain elusive. Here, we reveal a hitherto unknown function of human KAT2A (GCN5) as a histone acetyltransferase (HAT) of H2A.Z at the promoters of a set of transactivated genes. Expression of these genes also depends on the DNA repair complex XPC-RAD23-CEN2. We established that XPC-RAD23-CEN2 interacts both with H2A.Z and KAT2A to drive the recruitment of the HAT at promoters and license H2A.Z acetylation. KAT2A selectively acetylates H2A.Z.1 versus H2A.Z.2 in vitro on several well-defined lysines and we unveiled that alanine-14 in H2A.Z.2 is responsible for inhibiting the activity of KAT2A. Notably, the use of a nonacetylable H2A.Z.1 mutant shows that H2A.Z.1ac recruits the epigenetic reader BRD2 to promote RNA polymerase II recruitment. Our studies identify KAT2A as an H2A.Z.1 HAT in mammals and implicate XPC-RAD23-CEN2 as a transcriptional co-activator licensing the reshaping of the promoter epigenetic landscape.
Référence
Nat. Chem. Biol.. 2019 Sep 16;: