{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shen Z"],"funding":["National Institutes of Health","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["308-321"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11146590"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["38(7-8)"],"pubmed_abstract":["The transcription factor Oct4/Pou5f1 is a component of the regulatory circuitry governing pluripotency and is widely used to induce pluripotency from somatic cells. Here we used domain swapping and mutagenesis to study Oct4's reprogramming ability, identifying a redox-sensitive DNA binding domain, cysteine residue (Cys48), as a key determinant of reprogramming and differentiation. Oct4 Cys48 sensitizes the protein to oxidative inhibition of DNA binding activity and promotes oxidation-mediated protein ubiquitylation. <i>Pou5f1</i> <sup><i>C48S</i></sup> point mutation has little effect on undifferentiated embryonic stem cells (ESCs) but upon retinoic acid (RA) treatment causes retention of Oct4 expression, deregulated gene expression, and aberrant differentiation. <i>Pou5f1</i> <sup><i>C48S"],"journal":["Genes & development"],"pubmed_title":["Oct4 redox sensitivity potentiates reprogramming and differentiation."],"pmcid":["PMC11146590"],"funding_grant_id":["R01 GM122778","R01GM122778","R01 GM127783"],"pubmed_authors":["Cairns BR","Shen Z","Tantin D","Chandrasekharan MB","Evason KJ","Manna A","Yi C","Wu Y"],"additional_accession":[]},"is_claimable":false,"name":"Oct4 redox sensitivity potentiates reprogramming and differentiation.","description":"The transcription factor Oct4/Pou5f1 is a component of the regulatory circuitry governing pluripotency and is widely used to induce pluripotency from somatic cells. Here we used domain swapping and mutagenesis to study Oct4's reprogramming ability, identifying a redox-sensitive DNA binding domain, cysteine residue (Cys48), as a key determinant of reprogramming and differentiation. Oct4 Cys48 sensitizes the protein to oxidative inhibition of DNA binding activity and promotes oxidation-mediated protein ubiquitylation. <i>Pou5f1</i> <sup><i>C48S</i></sup> point mutation has little effect on undifferentiated embryonic stem cells (ESCs) but upon retinoic acid (RA) treatment causes retention of Oct4 expression, deregulated gene expression, and aberrant differentiation. <i>Pou5f1</i> <sup><i>C48S","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-02T03:54:58.497Z","creation":"2025-04-26T19:34:12.483Z"},"accession":"S-EPMC11146590","cross_references":{"pubmed":["38719541"],"doi":["10.1101/gad.351411.123"]}}