{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:25:13Z","timestamp":1792761913370,"version":"4.5.0"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["JP22H03254,JP 21K19596,JP19K22708,JP 21H04841,JP 20K20475,JP 16H06393,JP16H06276"],"award-info":[{"award-number":["JP22H03254,JP 21K19596,JP19K22708,JP 21H04841,JP 20K20475,JP 16H06393,JP16H06276"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005865","name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"crossref","award":["Mochida Memorial Foundation for Medical"],"award-info":[{"award-number":["Mochida Memorial Foundation for Medical"]}],"id":[{"id":"10.13039\/501100005865","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005865","name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"crossref","award":["Pharmaceutical Research"],"award-info":[{"award-number":["Pharmaceutical Research"]}],"id":[{"id":"10.13039\/501100005865","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,10]]},"abstract":"<jats:p>\n                    The transcription factor SRY-related HMG box 9 (Sox9) is essential for chondrogenesis. Mutations in and around\n                    <jats:italic>SOX9<\/jats:italic>\n                    cause campomelic dysplasia (CD) characterized by skeletal malformations. Although the function of Sox9 in this context is well studied, the mechanisms that regulate Sox9 expression in chondrocytes remain to be elucidated. Here, we have used genome-wide profiling to identify 2 Sox9 enhancers located in a proximal breakpoint cluster responsible for CD. Enhancer activity of E308 (located 308 kb 5\u2032 upstream) and E160 (located 160 kb 5\u2032 upstream) correlated with Sox9 expression levels, and both enhancers showed a synergistic effect in vitro. While single deletions in mice had no apparent effect, simultaneous deletion of both E308 and E160 caused a dwarf phenotype, concomitant with a reduction of Sox9 expression in chondrocytes. Moreover, bone morphogenetic protein 2\u2013dependent chondrocyte differentiation of limb bud mesenchymal cells was severely attenuated in E308\/E160 deletion mice. Finally, we found that an open chromatin region upstream of the Sox9 gene was reorganized in the E308\/E160 deletion mice to partially compensate for the loss of E308 and E160. In conclusion, our findings reveal a mechanism of Sox9 gene regulation in chondrocytes that might aid in our understanding of the pathophysiology of skeletal disorders.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.175486","type":"journal-article","created":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T14:00:27Z","timestamp":1717941627000},"source":"Crossref","is-referenced-by-count":14,"title":["Chromatin profiling identifies chondrocyte-specific Sox9 enhancers important for skeletal development"],"prefix":"10.1172","volume":"9","author":[{"given":"Sachi","family":"Ichiyama-Kobayashi","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry,"},{"name":"Department of Oral and Maxillofacial Oncology and Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular 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