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RACK7 Interacts with PRC2 Complex to Regulate Astrocyte Development

delete2025-03-24
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OA
AI
F
Fangfang Jiao
T
Tianxiang Tang
B
Bowen Wang
S
S. He
Y
Y. Zhang
L
Li Dong
B
Bo Xu
Y
Ying Liu
朱
朱平 (Ping Zhu)
R
Rui Guo
DOI:10.1002/advs.202416350delete
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摘要

摘要

En 中文
表观遗传机制失调在脑发育和疾病中发挥关键作用。大量新兴证据表明,激活C-激酶7受体(RACK7),一种表观遗传读码蛋白,可能在脑发育和神经发育疾病中发挥作用,但体内探索仍不足。本研究建立了一种Rack7条件性敲除小鼠模型,并发现Rack7缺陷小鼠表现出与异常星形胶质细胞发育相关的明显发育缺陷。机制上,研究发现RACK7与组蛋白H3赖氨酸27(H3K27)甲基转移酶,即多梳抑制复合物2(PRC2)复合物相互作用,以确定Suppressor of Zeste 12同源物(SUZ12)和H3K27甲基化的基因组定位。在星形胶质细胞中敲除Rack7导致全基因组范围内H3K27me3染色质定位显著减少。此外,RACK7与H3K27me3协同作用以防止Wnt信号通路的过度激活,并发现其他星形胶质细胞分化基因。综上,本研究为RACK7调控的脑发育的细胞和分子机制提供了新的见解。
Keyword:
Astrocyte development
PRC2 complex
RACK7
Wnt signaling pathway
ZMYND8
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Advanced Science
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14.1
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Argonne Natl Lab
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Guangdong Prov Peoples Hosp
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princess nourah bint abdulrahman. university
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