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We demonstrate that the PRS region also strongly regulates\n            <jats:italic>Sox9<\/jats:italic>\n            in CNCC-derived Meckel\u2019s cartilage (MC), but not in limb cartilages, even after decommissioning of CNCC enhancers. Such an MC-specific regulatory effect correlates with the MC-specific chromatin contacts between the PRS region and\n            <jats:italic>Sox9<\/jats:italic>\n            , highlighting the importance of lineage-dependent chromatin topology in instructing enhancer usage. By integrating the enhancer signatures and chromatin topology, we uncovered &gt;10,000 enhancers that function differentially between MC and limb cartilages and demonstrated their association with human diseases. Our findings provide critical insights for understanding the choreography of gene regulation during development and interpreting the genetic basis of craniofacial pathologies.\n          <\/jats:p>","DOI":"10.1126\/sciadv.abo3648","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T18:59:28Z","timestamp":1669229968000},"source":"Crossref","is-referenced-by-count":12,"title":["Integration of 3D genome topology and local chromatin features uncovers enhancers underlying craniofacial-specific cartilage defects"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0313-6475","authenticated-orcid":true,"given":"Qiming","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7807-3582","authenticated-orcid":true,"given":"Jiewen","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China."},{"name":"Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7022-2213","authenticated-orcid":true,"given":"Qian","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China."},{"name":"Shanghai Institute of Precision Medicine, Shanghai, 200125, China."},{"name":"Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12753"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3682"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.09.018"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau0320"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11247"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2493-4"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3949"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.138"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03446-x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03145-z"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0060-8"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00349-7"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067799"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1181369"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0538-0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/8792"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1631288100"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.233247.113"},{"key":"e_1_3_3_20_2","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1002\/ajmg.a.36134","article-title":"A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild campomelic dysplasia and small patella syndrome","volume":"161","author":"Matsushita M.","year":"2013","unstructured":"M. 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