The stage-specific roles of HIF-1α in regulating mESC pluripotency during oxygen transition

Hypoxia-inducible factor 1-alpha (HIF-1α) is a key transcription factor in cellular responses to oxygen levels. This study investigated HIF-1α's binding dynamics to the genome during the transition from normoxia to hypoxia in mouse embryonic stem cells. Analyzing HIF-1α chromatin immunoprecipitation sequencing data under normoxia, acute hypoxia, and stable hypoxia revealed a "bind-release-bind" pattern, with the weakest binding during acute hypoxia and the strongest during stable hypoxia. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified distinct gene sets and pathways regulated by HIF-1α in these conditions, with significant effects on pluripotency under normoxia and stable hypoxia. HIF-1α also partnered with different transcription factors depending on the oxygen level, further influencing its functions. RNA-Seq data and knockdown experiments confirmed the essential role of HIF-1α in maintaining mouse embryonic stem cell pluripotency under normoxia and stable hypoxia, with minimal impact under acute hypoxia. These findings enhance our understanding the regulatory mechanisms of HIF-1α and its role in cellular hypoxic responses.