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Among the various HIF-1\u03b1 posttranslational modifications, HIF-1\u03b1 methylation and its physiological role have not yet been elucidated. Here we show that HIF-1\u03b1 is methylated by SET7\/9 methyltransferase, and that lysine-specific demethylase 1 reverses its methylation. The functional consequence of HIF-1\u03b1 methylation is the modulation of HIF-1\u03b1 stability primarily in the nucleus, independent of its proline hydroxylation, during long-term hypoxic and normoxic conditions. Knock-in mice bearing a methylation-defective\n                    <jats:italic>Hif1a<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>KA\/KA<\/jats:italic>\n                    <\/jats:sup>\n                    allele exhibit enhanced retinal angiogenesis and tumour vascularization via HIF-1\u03b1 stabilization. Importantly, S28Y and R30Q mutations of HIF-1\u03b1, found in human cancers, are involved in the altered HIF-1\u03b1 stability. Together, these results demonstrate a role for HIF-1\u03b1 methylation in regulating protein stability, thereby modulating biological output including retinal and tumour angiogenesis, with therapeutic implications in human cancer.\n                  <\/jats:p>","DOI":"10.1038\/ncomms10347","type":"journal-article","created":{"date-parts":[[2016,1,13]],"date-time":"2016-01-13T06:44:40Z","timestamp":1452667480000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":188,"title":["Methylation-dependent regulation of HIF-1\u03b1 stability restricts retinal and tumour angiogenesis"],"prefix":"10.1038","volume":"7","author":[{"given":"Yunho","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jin","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyeop","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Young","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9780-6155","authenticated-orcid":false,"given":"Chan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Suk","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongha","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Won","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhyuk","family":"Bhin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daehee","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1231-1485","authenticated-orcid":false,"given":"Gou Young","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Hee","family":"Baek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,13]]},"reference":[{"key":"BFncomms10347_CR1","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1002\/jcb.22956","volume":"112","author":"J Cassavaugh","year":"2011","unstructured":"Cassavaugh, J. & Lounsbury, K. 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