NIR is a novel INHAT repressor that modulates the transcriptional activity of p53.
Fiche publication
Date publication
décembre 2005
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VAN DORSSELAER Alain, Dr MIGUET Laurent
Tous les auteurs :
Hublitz P, Kunowska N, Mayer UP, Muller JM, Heyne K, Yin N, Fritzsche C, Poli C, Miguet L, Schupp IW, van Grunsven LA, Potiers N, van Dorsselaer A, Metzger E, Roemer K, Schule R
Lien Pubmed
Résumé
Most transcriptional repression pathways depend on the targeted deacetylation of histone tails. In this report, we characterize NIR, a novel transcriptional corepressor with inhibitor of histone acetyltransferase (INHAT) activity. NIR (Novel INHAT Repressor) is ubiquitously expressed throughout embryonic development and adulthood. NIR is a potent transcriptional corepressor that is not blocked by histone deacetylase inhibitors and is capable of silencing both basal and activator-driven transcription. NIR directly binds to nucleosomes and core histones and prevents acetylation by histone acetyltransferases, thus acting as a bona fide INHAT. Using a tandem affinity purification approach, we identified the tumor suppressor p53 as a NIR-interacting partner. Association of p53 and NIR was verified in vitro and in vivo. Upon recruitment by p53, NIR represses transcription of both p53-dependent reporters and endogenous target genes. Knock-down of NIR by RNA interference significantly enhances histone acetylation at p53-regulated promoters. Moreover, p53-dependent apoptosis is robustly increased upon depletion of NIR. In summary, our findings describe NIR as a novel INHAT that plays an important role in the control of p53 function.
Référence
Genes Dev. 2005 Dec 1;19(23):2912-24.