{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:03:54Z","timestamp":1789643034575,"version":"4.0.0"},"reference-count":67,"publisher":"Portland Press Ltd.","issue":"10","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206293\/Z\/17\/Z"],"award-info":[{"award-number":["206293\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"UKRI | Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["DTP"],"award-info":[{"award-number":["DTP"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypoxia-inducible factors (HIFs) are key regulators of cellular responses to low oxygen (hypoxia), controlling the expression of genes required for survival and adaptation. KDM2B, a chromatin-modifying enzyme, is a direct target of HIF-1\u03b1, but its precise role in regulating HIF and the hypoxia response remains unclear. Here, we investigated the role of KDM2B in the response to hypoxia in a variety of cell lines. Our analysis reveals that KDM2B depletion regulates HIF activity in a cell type-dependent manner, with KDM2B depletion decreasing HIF activity in U2OS and MDA-MB-231 cells and increasing HIF activity in HeLa cells. We show that KDM2B depletion also reduces HIF-1\u03b1 protein and RNA expression and reduces HIF-1\u03b1 binding at hypoxia-response elements of its target genes in U2OS and MDA-MB-231 cells. Conversely, overexpression of KDM2B enhances HIF activity and HIF-1\u03b1 levels in both U2OS and HEK293 cells. Mechanistically, we find that KDM2B requires its jumonji-C demethylase and CxxC DNA-binding domains for HIF regulation. Furthermore, we demonstrate that KDM2B is required for RNA Pol II recruitment to the promoter of HIF1A. At the cellular level, KDM2B supports cell proliferation, with its depletion impairing proliferation and reducing cell numbers under hypoxic conditions. Our work highlights a new function of KDM2B as a key regulator of HIF-1\u03b1 expression, acting through its demethylase and DNA-binding functions. Our data indicate that KDM2B is essential for cellular adaptation to hypoxia, impacting both HIF-dependent gene expression and cell survival, and has important implications for our understanding of HIF regulation.<\/jats:p>","DOI":"10.1042\/bcj20260212","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:27:50Z","timestamp":1788776870000},"page":"1979-1997","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["KDM2B controls HIF levels and activity through its JmjC and CxxC domains"],"prefix":"10.1042","volume":"483","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7508-6641","authenticated-orcid":false,"given":"Michael","family":"Batie","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L697ZB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8045-5421","authenticated-orcid":false,"given":"Dilem","family":"Shakir","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L697ZB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Sui","family":"Kwok","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L697ZB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L697ZB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahua","family":"Kou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L697ZB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Bakhsh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L697ZB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-4981","authenticated-orcid":false,"given":"Sonia","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L697ZB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"2026091706365668100_B1","doi-asserted-by":"publisher","first-page":"eaba3512","DOI":"10.1126\/science.aba3512","article-title":"Oxygen-sensing mechanisms across eukaryotic kingdoms and their roles in complex multicellularity","volume":"370","author":"Hammarlund","year":"2020","journal-title":"Science"},{"key":"2026091706365668100_B2","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/s41580-020-0227-y","article-title":"Cellular adaptation to hypoxia through hypoxia inducible factors and beyond","volume":"21","author":"Lee","year":"2020","journal-title":"Nat. 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