Functional interplay between TFIIH and KAT2A regulates higher-order chromatin structure and class II gene expression - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2019

Functional interplay between TFIIH and KAT2A regulates higher-order chromatin structure and class II gene expression

Résumé

The TFIIH subunit XPB is involved in combined Xeroderma Pigmentosum and Cockayne syndrome (XP-B/CS). Our analyses reveal that XPB interacts functionally with KAT2A, a histone acetyltransferase (HAT) that belongs to the hSAGA and hATAC complexes. XPB interacts with KAT2A-containing complexes on chromatin and an XP-B/CS mutation specifically elicits KAT2A-mediated large-scale chromatin decondensation. In XP-B/CS cells, the abnormal recruitment of TFIIH and KAT2A to chromatin causes inappropriate acetylation of histone H3K9, leading to aberrant formation of transcription initiation complexes on the promoters of several hundred genes and their subsequent overexpression. Significantly, this cascade of events is similarly sensitive to KAT2A HAT inhibition or to the rescue with wild-type XPB. In agreement, the XP-B/CS mutation increases KAT2A HAT activity in vitro. Our results unveil a tight connection between TFIIH and KAT2A that controls higher-order chromatin structure and gene expression and provide new insights into transcriptional mis-regulation in a cancer-prone DNA repair-deficient disorder.
Fichier principal
Vignette du fichier
s41467-019-09270-2.pdf (3.27 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02348130 , version 1 (09-11-2020)

Identifiants

Citer

Jérémy Sandoz, Zita Nagy, Philippe Catez, Gizem Caliskan, Sylvain Geny, et al.. Functional interplay between TFIIH and KAT2A regulates higher-order chromatin structure and class II gene expression. Nature Communications, 2019, 10 (1), ⟨10.1038/s41467-019-09270-2⟩. ⟨hal-02348130⟩
77 Consultations
39 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More