NIR is a novel INHAT repressor that modulates the transcriptional activity of p53
- 1 December 2005
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 19 (23), 2912-2924
- https://doi.org/10.1101/gad.351205
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.Keywords
This publication has 39 references indexed in Scilit:
- Direct p53 Transcriptional Repression: In Vivo Analysis of CCAAT-Containing G2/M PromotersMolecular and Cellular Biology, 2005
- Characterization of Four Autonomous Repression Domains in the Corepressor Receptor Interacting Protein 140Published by Elsevier BV ,2004
- Remodelling chromatin on a global scale: a novel protective function of p53Carcinogenesis: Integrative Cancer Research, 2004
- p53 Functions through Stress- and Promoter-Specific Recruitment of Transcription Initiation Components before and after DNA DamageMolecular Cell, 2003
- The Activation Domains, the Proline-rich Domain, and the C-terminal Basic Domain in p53 Are Necessary for Acetylation of Histones on the Proximal p21 Promoter and Interaction with p300/CREB-binding ProteinPublished by Elsevier BV ,2003
- Ikaros-CtIP Interactions Do Not Require C-terminal Binding Protein and Participate in a Deacetylase-independent Mode of RepressionPublished by Elsevier BV ,2002
- p53 Amino Acids 339–346 Represent the Minimal p53 Repression DomainPublished by Elsevier BV ,2001
- The language of covalent histone modificationsNature, 2000
- The Transcriptional Coactivators p300 and CBP Are Histone AcetyltransferasesCell, 1996
- Nucleosome arrays inhibit both initiation and elongation of transcripts by bacteriophage T7 RNA polymeraseJournal of Molecular Biology, 1992