HIF-dependent and reversible nucleosome disassembly in hypoxia-inducible gene promoters

Norio Suzuki, Nikola Vojnovic, Kian Leong Lee, Henry Yang, Katarina Gradin, Lorenz Poellinger

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Hypoxia causes dramatic changes in gene expression profiles, and the mechanism of hypoxia-inducible transcription has been analyzed for use as a model system of stress-inducible gene regulation. In this study, changes in chromatin organization in promoters of hypoxia-inducible genes were investigated during hypoxia-reoxygenation conditions. Most of the hypoxia-inducible gene promoters were hypersensitive to DNase I under both normal and hypoxic conditions, and our data indicate an immediate recruitment of transcription factors under hypoxic conditions. In some of the hypoxia-inducible promoters, nucleosome-free DNA regions (NFRs) were established in parallel with hypoxia-induced transcription. We also show that the hypoxia-inducible formation of NFRs requires that hypoxia-inducible transcription factors (HIFs) bind to the promoters together with the transcriptional coactivator CBP. Within 1 h after the hypoxia exposure was ended (reoxygenation), HIF complexes were dissociated from the promoter regions. Within 24 h of reoxygenation, the hypoxia-induced transcription returned to basal levels and the nucleosome structure was reassembled in the hypoxia-inducible NFRs. Nucleosome reassembly required the function of the transcriptional coregulator SIN3A. Thus, reversible changes in nucleosome organization mediated by transcription factors are notable features of stress-inducible gene regulation.

Original languageEnglish
Pages (from-to)181-191
Number of pages11
JournalExperimental Cell Research
Volume366
Issue number2
DOIs
Publication statusPublished - 2018 May 15

Keywords

  • Chromatin
  • Hypoxia-inducible transcription
  • Nucleosome-free region

ASJC Scopus subject areas

  • Cell Biology

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