title: NIR is a novel INHAT repressor that modulates the transcriptional activity of p53.
abstract: 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.
authors.affiliation: Frauenklinik der Albert-Ludwigs-Universität Freiburg, Zentrale Klinische Forschung, D-79106 Freiburg, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Hublitz
authors.forename: Natalia
authors.initials: N
authors.lastname: Kunowska
authors.forename: Ulrich P
authors.initials: UP
authors.lastname: Mayer
authors.forename: Judith M
authors.initials: JM
authors.lastname: Müller
authors.forename: Kristina
authors.initials: K
authors.lastname: Heyne
authors.forename: Na
authors.initials: N
authors.lastname: Yin
authors.forename: Claudia
authors.initials: C
authors.lastname: Fritzsche
authors.forename: Cecilia
authors.initials: C
authors.lastname: Poli
authors.forename: Laurent
authors.initials: L
authors.lastname: Miguet
authors.forename: Ingo W
authors.initials: IW
authors.lastname: Schupp
authors.forename: Leo A
authors.initials: LA
authors.lastname: van Grunsven
authors.forename: Noëlle
authors.initials: N
authors.lastname: Potiers
authors.forename: Alain
authors.initials: A
authors.lastname: van Dorsselaer
authors.forename: Eric
authors.initials: E
authors.lastname: Metzger
authors.forename: Klaus
authors.initials: K
authors.lastname: Roemer
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
mesh_terms: D000818:Animals; D017209:Apoptosis; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D034622:RNA Interference; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: C507221:NIR protein, mouse; C507220:NOC2L protein, human; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D051548:Histone Acetyltransferases