Yayınlanmış 1 Ocak 2019
| Sürüm v1
Dergi makalesi
Açık
Functional interplay between TFIIH and KAT2A regulates higher-order chromatin structure and class II gene expression
Oluşturanlar
- 1. Museum Natl Hist Nat, Lab Struct & Instabilite Genomes, CNRS UMR7196, INSERM U1154, 43 Rue Cuvier, F-75005 Paris, France
Açıklama
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 wildtype 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 misregulation in a cancer-prone DNA repair-deficient disorder.
Dosyalar
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Dosyalar
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