2. Academic Validation
  3. DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during transcription

DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during transcription

  • Nat Chem Biol. 2019 Oct;15(10):992-1000. doi: 10.1038/s41589-019-0354-y.
M Semer 1 2 3 4,  B Bidon 1 2 3 4,  A Larnicol 1 2 3 4,  G Caliskan 1 2 3 4 5,  P Catez 1 2 3 4,  J M Egly 1 2 3 4,  F Coin 6 7 8 9,  N Le May 10 11 12 13
Affiliations

Affiliations

  • 1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, Equipe Labélisée Ligue contre le Cancer, Illkirch Cedex, Strasbourg, France.
  • 2 Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.
  • 3 Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France.
  • 4 Université de Strasbourg, Illkirch, France.
  • 5 Department of Pharmaceutical Biotechnology, Faculty of pharmacy, Sivas Cumhuriyet University, Sivas, Turkey.
  • 6 Institut de Génétique et de Biologie Moléculaire et Cellulaire, Equipe Labélisée Ligue contre le Cancer, Illkirch Cedex, Strasbourg, France. [email protected].
  • 7 Centre National de la Recherche Scientifique, UMR7104, Illkirch, France. [email protected].
  • 8 Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France. [email protected].
  • 9 Université de Strasbourg, Illkirch, France. [email protected].
  • 10 Institut de Génétique et de Biologie Moléculaire et Cellulaire, Equipe Labélisée Ligue contre le Cancer, Illkirch Cedex, Strasbourg, France. [email protected].
  • 11 Centre National de la Recherche Scientifique, UMR7104, Illkirch, France. [email protected].
  • 12 Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, France. [email protected].
  • 13 Université de Strasbourg, Illkirch, France. [email protected].
PMID: 31527837 DOI: 10.1038/s41589-019-0354-y
Abstract

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.

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