Hypoxia induces a novel signature of chromatin modifications and global repression of transcription

Mutat Res. 2008 Apr 2;640(1-2):174-9. doi: 10.1016/j.mrfmmm.2008.01.001. Epub 2008 Jan 16.


Tumor cells respond to the harsh hypoxic microenvironment, in part, by transcriptional regulation of specific target genes. We found that hypoxia-mediated activation of selected genes occurs amidst widespread repression of transcription that is neither cell type-specific nor HIF-1-dependent. Despite overall repression, hypoxia induces a pool of histone modifications typically associated with transcriptional activation or repression. Chromatin immunoprecipitation analyses showed that this global mixture of hypoxia-modified histones is sorted in a gene-specific manner to correlate with transcriptional response to hypoxia. Exceptions to this were unexpected increases in H3K4me3 levels, typically associated with transcriptional activation, and decreased H3K27me3 levels, generally a marker of transcriptional silencing, at core promoters of both hypoxia-activated and -repressed genes. These data suggest that a novel signature of chromatin modifications is induced under hypoxic stress, which may play a role in gene regulatory switches active in proliferating tumor cells undergoing cycles of hypoxia and reoxygenation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Hypoxia / genetics*
  • Cell Line, Tumor
  • Chromatin Assembly and Disassembly*
  • Gene Expression Regulation, Neoplastic*
  • Histones / metabolism
  • Hypoxia-Inducible Factor 1 / metabolism
  • Mice
  • RNA / biosynthesis
  • RNA, Messenger / biosynthesis
  • Transcription, Genetic*


  • Histones
  • Hypoxia-Inducible Factor 1
  • RNA, Messenger
  • RNA