LAUSR

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. Graphical abstract Figure. No caption available. HighlightsNucleosome‐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.