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This lineage commitment is governed by complex transcription factor networks. RUNX2 and KLF4, known key TFs co\u2010expressed in this process, were proven to operate synergistically, but the specific cofactors coordinating their activity at the chromatin level remain unknown. Here, we identify the chromatin remodeller BRD9 as a novel interactor of both RUNX2 and KLF4 during odontoblastic differentiation. To probe their shared function, we generated neural crest\u2010specific conditional knockout mice.\n                    <jats:italic>Wnt1<\/jats:italic>\n                    \u2010Cre;\n                    <jats:italic>Brd9<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    mice exhibited a disordered odontoblast layer with reduced secretion of extracellular matrix proteins (DMP1 and DSPP), strikingly phenocopying the compound\n                    <jats:italic>Wnt1<\/jats:italic>\n                    \u2010Cre;\n                    <jats:italic>Runx2<\/jats:italic>\n                    <jats:sup>fl\/wt<\/jats:sup>\n                    ;\n                    <jats:italic>Klf4<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    mutants. In\u00a0vitro, chemical BRD9 degradation suppressed odontoblastic differentiation and mineral deposition. Integrative analyses of RNA\u2010seq and ATAC\u2010seq revealed that BRD9 maintained chromatin accessibility at odontogenesis\u2010associated regions enriched with RUNX2 and KLF4 motifs, specifically at the\n                    <jats:italic>Fam20c<\/jats:italic>\n                    enhancer, thereby facilitating RUNX2 and KLF4 binding for transcriptional activation. Crucially, exogenous supplementation of FAM20C protein partially rescued the odontoblastic differentiation defects upon BRD9 loss. These findings establish BRD9 as a critical epigenetic orchestrator that coordinates RUNX2\u2010KLF4 synergy to activate key odontogenic genes like\n                    <jats:italic>Fam20c<\/jats:italic>\n                    , thus affecting odontoblastic differentiation and dentinogenesis.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70269","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T13:03:43Z","timestamp":1786021423000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chromatin Remodeller\n                    <scp>BRD9<\/scp>\n                    Orchestrates Odontoblastic Differentiation via Coordinating\n                    <scp>RUNX2<\/scp>\n                    \u2010\n                    <scp>KLF4<\/scp>"],"prefix":"10.1111","author":[{"given":"Wenrui","family":"Zeng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiu","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Department of Cariology and Endodontics, School of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyan","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delan","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment Stomatological Hospital of Xiamen Medical College  Xiamen 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Developmentally Originated Disease  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9947-6687","authenticated-orcid":false,"given":"Huan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Frontier Science Center for Immunology and Metabolism Wuhan University  Wuhan China"},{"name":"TaiKang Center for Life and Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-1324","authenticated-orcid":false,"given":"Zhi","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of 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