Chromatin Remodeller BRD9 Orchestrates Odontoblastic Differentiation via Coordinating RUNX2-KLF4.

Overview

1. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
2. Department of Cariology and Endodontics, School of Stomatology, Wuhan University, Wuhan, China
3. Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Stomatological Hospital of Xiamen Medical College, Xiamen, China
4. Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China
5. Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China
6. TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China

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; Brd9 fl/fl mice exhibited a disordered odontoblast layer with reduced secretion of extracellular matrix proteins (DMP1 and DSPP), strikingly phenocopying the compound Wnt1‐Cre; Runx2 fl/wt; Klf4 fl/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.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSM5700359 — at NCBI GEO; found in the text, “Chromatin Remodeller BRD9 Interacts With RUNX2…”

Data Availability Statement

The data that support the findings of this study are openly available in Genome Sequence Archive at https://ngdc.cncb.ac.cn/gsa [59, 60], reference number CRA036150.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, pages, dates, 9 authors, 6 keywords, 2 funders, 60 references.

Cite

This paper

Zeng, W., Lin, Y., Gao, Y., Huang, D., Li, Y., Ruan, H., Yuan, G., Liu, H., & Chen, Z. (2026). Chromatin Remodeller BRD9 Orchestrates Odontoblastic Differentiation via Coordinating RUNX2-KLF4. Cell proliferation, e70269. https://doi.org/10.1111/cpr.70269

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