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PMID:16322561
| Citation |
Hublitz, P, Kunowska, N, Mayer, UP, Müller, 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 and Schüle, R (2005) NIR is a novel INHAT repressor that modulates the transcriptional activity of p53. Genes Dev. 19:2912-24 |
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| 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. |
| Links |
PubMed PMC1315397 Online version:10.1101/gad.351205 |
| Keywords |
Animals; Apoptosis; Gene Expression Regulation; Histone Acetyltransferases/antagonists & inhibitors; Humans; Mice; Mice, Knockout; Promoter Regions, Genetic; Protein Interaction Mapping; RNA Interference; Repressor Proteins/metabolism; Repressor Proteins/physiology; Transcription, Genetic; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism |
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Significance
Annotations
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