Authors
Wenrui Zeng, Yuxiu Lin, Yongyan Gao, Delan Huang, Yuanyuan Li, Honglei Ruan, Guohua Yuan, Huan Liu, Zhi Chen
Published in
Cell proliferation. Pages e70269. Aug 06, 2026. Epub Aug 06, 2026.
Abstract
Dentinogenesis, a process essential for tooth function, relies on the precise differentiation of dental papilla cells into odontoblasts. This lineage commitment is governed by complex transcription factor networks. RUNX2 and KLF4, known key TFs co-expressed 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-specific conditional knockout mice. Wnt1-Cre; Brd9fl/fl mice exhibited a disordered odontoblast layer with reduced secretion of extracellular matrix proteins (DMP1 and DSPP), strikingly phenocopying the compound Wnt1-Cre; Runx2fl/wt; Klf4fl/fl mutants. In vitro, chemical BRD9 degradation suppressed odontoblastic differentiation and mineral deposition. Integrative analyses of RNA-seq and ATAC-seq revealed that BRD9 maintained chromatin accessibility at odontogenesis-associated regions enriched with RUNX2 and KLF4 motifs, specifically at the Fam20c 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-KLF4 synergy to activate key odontogenic genes like Fam20c, thus affecting odontoblastic differentiation and dentinogenesis.
PMID:
42560112
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.
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