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

• Published in: Experimental cell research Vol. 366; no. 2; pp. 181 - 191
• Main Authors: Suzuki, Norio, Vojnovic, Nikola, Lee, Kian-Leong, Yang, Henry, Gradin, Katarina, Poellinger, Lorenz
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.05.2018
• Subjects: 60 APPLIED LIFE SCIENCES; ANOXIA; Chromatin; GENE REGULATION; Hypoxia-inducible transcription; Medicin och hälsovetenskap; Nucleosome-free region; NUCLEOSOMES; TRANSCRIPTION FACTORS; Nucleosome-free region; Chromatin; Hypoxia-inducible transcription
• ISSN: 0014-4827; 1090-2422; 1090-2422
• DOI: 10.1016/j.yexcr.2018.03.020

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. [Display omitted] •Nucleosome-free regions (NFRs) are established in some gene promoters in a hypoxia-dependent manner.•Hypoxia-inducible NFR (iNFR) formation requires hypoxia-inducible transcription factor (HIF) activity.•Reoxygenation induces the reassembly of nucleosome structures in iNFRs.•Nucleosome reassembly in iNFRs requires SIN3A.