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

ARID1A safeguards the canalization of the cell fate decision during osteoclastogenesis

Nat Commun. 2024 Jul 17;15(1):5994. doi: 10.1038/s41467-024-50225-z.

Authors

Jiahui Du^#^{1

2

3}, Yili Liu^#^{1

2

3}, Jinrui Sun^#^{1

2

3}, Enhui Yao^#^{1

2

3}, Jingyi Xu^{1

2

3}, Xiaolin Wu^{1

2

3}, Ling Xu^{1

2

3}, Mingliang Zhou^{1

2

3}, Guangzheng Yang^{4

5

6}, Xinquan Jiang^{7

8

9}

Affiliations

¹ Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
³ National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai, China.
⁴ Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
⁵ College of Stomatology, Shanghai Jiao Tong University, Shanghai, China. [email protected].
⁶ National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai, China. [email protected].
⁷ Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
⁸ College of Stomatology, Shanghai Jiao Tong University, Shanghai, China. [email protected].
⁹ National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai, China. [email protected].

^# Contributed equally.

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.

MeSH terms

Animals
Bromodomain Containing Proteins
Cell Differentiation*
Cell Lineage*
Cell Proliferation
Chromatin Assembly and Disassembly
DNA-Binding Proteins* / genetics
DNA-Binding Proteins* / metabolism
Gene Expression Regulation
Mice
Mice, Inbred C57BL
NFATC Transcription Factors / genetics
NFATC Transcription Factors / metabolism
Nuclear Proteins
Osteoclasts* / cytology
Osteoclasts* / metabolism
Osteogenesis* / genetics
Osteogenesis* / physiology
Single-Cell Analysis
Transcription Factors* / genetics
Transcription Factors* / metabolism

Substances

Transcription Factors
Arid1a protein, mouse
DNA-Binding Proteins
NFATC Transcription Factors
Brd4 protein, mouse
Nfatc1 protein, mouse
Bromodomain Containing Proteins
Nuclear Proteins

Abstract

MeSH terms

Substances

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