The Stage-Specific Roles of HIF-1α in Regulating mESCs 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 (mESCs). Analyzing HIF-1α ChIP-seq 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 (GO) and KEGG 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 HIF-1α's essential role in maintaining mESCs pluripotency under normoxia and stable hypoxia, with minimal impact under acute hypoxia. These findings enhance our understanding of HIF-1α's regulatory mechanisms and its role in cellular hypoxic responses.