ARID1A safeguards the canalization of the cell fate decision during osteoclastogenesis

Jiahui Du; Yili Liu; Jinrui Sun; Enhui Yao; Jingyi Xu; Xiaolin Wu; Ling Xu; Mingliang Zhou; Guangzheng Yang; Xinquan Jiang

doi:10.1038/s41467-024-50225-z

Nature Communications (Jul 2024)

ARID1A safeguards the canalization of the cell fate decision during osteoclastogenesis

Jiahui Du,
Yili Liu,
Jinrui Sun,
Enhui Yao,
Jingyi Xu,
Xiaolin Wu,
Ling Xu,
Mingliang Zhou,
Guangzheng Yang,
Xinquan Jiang

Affiliations

Jiahui Du: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Yili Liu: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Jinrui Sun: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Enhui Yao: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Jingyi Xu: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Xiaolin Wu: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Ling Xu: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Mingliang Zhou: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Guangzheng Yang: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Xinquan Jiang: Department of Prosthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine

DOI: https://doi.org/10.1038/s41467-024-50225-z
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 20

Abstract

Read online

Abstract Chromatin remodeler ARID1A regulates gene transcription by modulating nucleosome positioning and chromatin accessibility. While ARID1A-mediated stage and lineage-restricted gene regulation during cell fate canalization remains unresolved. Using osteoclastogenesis as a model, we show that ARID1A transcriptionally safeguards the osteoclast (OC) fate canalization during proliferation-differentiation switching at single-cell resolution. Notably, ARID1A is indispensable for the transcriptional apparatus condensates formation with coactivator BRD4/lineage-specifying transcription factor (TF) PU.1 at Nfatc1 super-enhancer during safeguarding the OC fate canalization. Besides, the antagonist function between ARID1A-cBAF and BRD9-ncBAF complex during osteoclastogenesis has been validated with in vitro assay and compound mutant mouse model. Furthermore, the antagonistic function of ARID1A-“accelerator” and BRD9-“brake” both depend on coactivator BRD4-“clutch” during osteoclastogenesis. Overall, these results uncover sophisticated cooperation between chromatin remodeler ARID1A, coactivator, and lineage-specifying TF at super-enhancer of lineage master TF in a condensate manner, and antagonist between distinct BAF complexes in the proper and balanced cell fate canalization.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

About the journal