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During this process, chondrocytes undergo multiple steps of differentiation and coordinated transition from a proliferating to a hypertrophic stage, which is critical to advance skeletal development. Here, we identified the transcription factor\n                    <jats:italic>Dmrt2<\/jats:italic>\n                    (double-sex and mab-3 related transcription factor 2) as a Sox9-inducible gene that promotes chondrocyte hypertrophy in pre-hypertrophic chondrocytes. Epigenetic analysis further demonstrated that Sox9 regulates\n                    <jats:italic>Dmrt2<\/jats:italic>\n                    expression through an active enhancer located 18\u2009kb upstream of the\n                    <jats:italic>Dmrt2<\/jats:italic>\n                    gene and that this enhancer\u2019s chromatin status is progressively activated through chondrocyte differentiation.\n                    <jats:italic>Dmrt2<\/jats:italic>\n                    -knockout mice exhibited a dwarf phenotype with delayed initiation of chondrocyte hypertrophy. Dmrt2 augmented hypertrophic chondrocyte gene expression including\n                    <jats:italic>Ihh<\/jats:italic>\n                    through physical and functional interaction with Runx2. Furthermore, Dmrt2 deficiency reduced Runx2-dependent\n                    <jats:italic>Ihh<\/jats:italic>\n                    expression. Our findings suggest that Dmrt2 is critical for sequential chondrocyte differentiation during endochondral bone formation and coordinates the transcriptional network between Sox9 and Runx2.\n                  <\/jats:p>","DOI":"10.1038\/s42003-021-01848-1","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T06:03:52Z","timestamp":1615442632000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Dmrt2 promotes transition of endochondral bone formation by linking Sox9 and Runx2"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-1481","authenticated-orcid":false,"given":"Koichiro","family":"Ono","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4367-9343","authenticated-orcid":false,"given":"Kenji","family":"Hata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Ishihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshifumi","family":"Takahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5021-5494","authenticated-orcid":false,"given":"Tomohiko","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Takenoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihisa","family":"Komori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7279-8363","authenticated-orcid":false,"given":"Riko","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Yoneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"1848_CR1","doi-asserted-by":"publisher","first-page":"a008334","DOI":"10.1101\/cshperspect.a008334","volume":"5","author":"F Long","year":"2013","unstructured":"Long, F. & Ornitz, D. 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