Regulation of chromatin accessibility by hypoxia and HIF
Open Access
- 28 March 2022
- journal article
- research article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 479 (6), 767-786
- https://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) coordinate a transcriptional programme required for survival and adaptation to hypoxia. The effects of HIF on chromatin accessibility landscape are still 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.Keywords
This publication has 61 references indexed in Scilit:
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- Fast gapped-read alignment with Bowtie 2Nature Methods, 2012
- Chromatin as an oxygen sensor and active player in the hypoxia responseCellular Signalling, 2012
- Differential oestrogen receptor binding is associated with clinical outcome in breast cancerNature, 2012
- The chromatin remodeler ISWI regulates the cellular response to hypoxia: role of FIHMolecular Biology of the Cell, 2011
- Integrative genomics viewerNature Biotechnology, 2011
- Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell IdentitiesMolecular Cell, 2010
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009
- Oxygen Sensing by Metazoans: The Central Role of the HIF Hydroxylase PathwayMolecular Cell, 2008
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005