The TORC1 activates Rpd3L complex to deacetylate Ino80 and H2A.Z and repress autophagy

被引:8
作者
Li, Xin [1 ]
Mei, Qianyun [1 ]
Yu, Qi [1 ]
Wang, Min [2 ]
He, Fei [1 ]
Xiao, Duncheng [1 ]
Liu, Huan [1 ]
Ge, Feng [2 ]
Yu, Xilan [1 ]
Li, Shanshan [1 ]
机构
[1] Hubei Univ, Sch Life Sci, State Key Lab Biocatalysis & Enzyme Engn, Wuhan 430062, Hubei, Peoples R China
[2] Chinese Acad Sci, Inst Hydrobiol, Key Lab Algal Biol, Wuhan 430072, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
multiple levels; including transcriptional; posttranscriptional; trans; HISTONE VARIANT H2A.Z; TRANSCRIPTIONAL REGULATION; SIGNALING CASCADE; ACETYLATION; RECRUITMENT; EXPRESSION; UME6; METHYLATION; MACHINERY; MECHANISM;
D O I
10.1126/sciadv.ade8312
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Autophagy is a critical process to maintain homeostasis, differentiation, and development. How autophagy is tightly regulated by nutritional changes is poorly understood. Here, we identify chromatin remodeling protein Ino80 and histone variant H2A.Z as the deacetylation targets for histone deacetylase Rpd3L complex and uncover how they regulate autophagy in response to nutrient availability. Mechanistically, Rpd3L deacetylates Ino80 K929, which protects Ino80 from being degraded by autophagy. The stabilized Ino80 promotes H2A.Z eviction from autophagy-related genes, leading to their transcriptional repression. Meanwhile, Rpd3L deacety-lates H2A.Z, which further blocks its deposition into chromatin to repress the transcription of autophagy-related genes. Rpd3-mediated deacetylation of Ino80 K929 and H2A.Z is enhanced by the target of rapamycin complex 1 (TORC1). Inactivation of TORC1 by nitrogen starvation or rapamycin inhibits Rpd3L, leading to induction of autophagy. Our work provides a mechanism for chromatin remodelers and histone variants in modulating au-tophagy in response to nutrient availability.
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页数:17
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