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Exp Cell Res. 2018 May 15;366(2):181-191. doi: 10.1016/j.yexcr.2018.03.020. Epub 2018 Mar 21.

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

Author information

1
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden; Division of Oxygen Biology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: sunorio@med.tohoku.ac.jp.
2
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
3
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Republic of Singapore.
4
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Republic of Singapore.

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.

KEYWORDS:

Chromatin; Hypoxia-inducible transcription; Nucleosome-free region

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