NIR is a novel INHAT repressor that modulates the transcriptional activity of p53

Genes Dev. 2005 Dec 1;19(23):2912-24. doi: 10.1101/gad.351205.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • NIR protein, mouse
  • NOC2L protein, human
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • Histone Acetyltransferases