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journal article·2025-05Open access

RACK7 Interacts with PRC2 Complex to Regulate Astrocyte Development

Fangfang Jiao, Tianxiang Tang, Bowen Wang, Shengfei He, Yue Zhang, Li Dong, Bo Xu, Ying Liu, Ping Zhu, Rui Guo

Advanced Science· Volume 12· Issue 19
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Source abstract

Abstract

Abstract Dysregulation of epigenetic mechanisms plays a crucial role in brain development and disease. Emerging largely evidence suggests that Receptor for Activated C‐kinase 7 (RACK7), an epigenetic reader protein, may play a role in brain development and neural developmental disease, but in vivo explorations are still lacking. Here, a Rack7 conditional knock‐out mouse model is established and shows that Rack7‐deficient mice exhibit overt developmental defects associated with aberrant astrocyte development. Mechanistically, it is found that RACK7 interacts with the histone H3 lysine 27 (H3K27) methyltransferase, i.e., the Polycomb Repressive Complex 2 (PRC2) complex, to establish the genomic locations of Suppressor of Zeste 12 homolog (SUZ12) and H3K27 methylation. Deletion of Rack7 in astrocytes leads to a remarkable decrease of H3K27me3 chromatin localization genome‐wide. Furthermore, RACK7 works together with H3K27me3 to prevent overactivation of the Wnt signaling pathway and other astrocyte differentiation genes are found. Collectively, this study provides new insights into the cellular and molecular mechanisms underlying brain development regulated by RACK7.
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Research context

OpenAlex topics: Epigenetics and DNA Methylation · Genetics and Neurodevelopmental Disorders · RNA modifications and cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Center for Medical Research and Innovation Shanghai Pudong Hospital Fudan University Pudong Medical Center and the Shanghai Key Laboratory of Medical Epigenetics the International Co‐laboratory of Medical Epigenetics and Metabolism Ministry of Science and Technology Institutes of Biomedical Sciences Fudan University Shanghai 200032 China

State Key Laboratory of Eye Health Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200011 China

Center for Excellence in Brain Science and Intelligence Technology (Institute of Neuroscience) Chinese Academy of Sciences 320 Yue Yang Road Shanghai 200031 China

Institutes of Biomedical Sciences Fudan University Shanghai 200032 China

Guangdong Cardiovascular Institute Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou Guangdong 510100 China

Department of Animal Dairy and Veterinary Sciences Utah State University Logan UT 84322 USA

Aging and Longevity Institute & Institute of Biological Science Zhongshan Hospital Fudan University Shanghai 200032 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · China Postdoctoral Science Foundation

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