Regulation of chromatin accessibility by hypoxia and HIF

Batie, Michael ORCID: 0000-0002-7508-6641, Frost, Julianty ORCID: 0000-0001-8209-2575, Shakir, Dilem and Rocha, Sonia (2022) Regulation of chromatin accessibility by hypoxia and HIF. BIOCHEMICAL JOURNAL, 479 (6). pp. 767-786.

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Official URL: http://dx.doi.org/10.1042/bcj20220008

Abstract

Reduced oxygen availability (hypoxia) can act as a signalling cue in physiological processes such as development, but also in pathological conditions such as cancer or ischaemic disease. As such, understanding how cells and organisms respond to hypoxia is of great importance. The family of transcription factors called Hypoxia Inducible Factors (HIFs) co-ordinate a transcriptional programme required for survival and adaptation to hypoxia. However, the effects of HIF on chromatin accessibility are currently unclear. Here, using genome wide mapping of chromatin accessibility via ATAC-seq, we find hypoxia induces loci specific changes in chromatin accessibility are enriched at a subset hypoxia transcriptionally responsive genes, agreeing with previous data using other models. We show for the first time that hypoxia inducible changes in chromatin accessibility across the genome are predominantly HIF dependent, rapidly reversible upon reoxygenation and partially mimicked by HIF-α stabilisation independent of molecular dioxygenase inhibition. This work demonstrates that HIF is central to chromatin accessibility alterations in hypoxia, and has implications for our understanding of gene expression regulation by hypoxia and HIF.

Item Type:	Article
Uncontrolled Keywords:	Chromatin, Humans, Oxygen, Cell Hypoxia, Gene Expression Regulation, Hypoxia-Inducible Factor 1, alpha Subunit, Hypoxia
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	25 Apr 2022 12:11
Last Modified:	18 Jan 2023 21:04
DOI:	10.1042/BCJ20220008
Open Access URL:	https://portlandpress.com/biochemj/article/479/6/7...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3153667