Core factor of NEXT complex,ZCCHC8,governs the silencing of LINE1 during spermatogenesis  

作　　者：Rushuang Yan Meijie Qi Pengfei Zhang Bin Shen Jiqing Yin Chuan Chen Silin Tian Lin Chen Xingxu Huang Hong Wang Shaorong Gao You Wu Yawei Gao 

机构地区：[1]State Key Laboratory of Cardiology and Medical Innovation Center,Department of Reproductive Medicine Center,Shanghai East Hospital,Frontier Science Center for Stem Cell Research,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China [2]Clinical and Translation Research Center of Shanghai First Maternity&Infant Hospital,Frontier Science Center for Stem Cell Research,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China [3]Reproductive and Genetic Center,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China [4]State Key Laboratory of Reproductive Medicine and Offspring Health,Women’s Hospital of Nanjing Medical University,Nanjing Women and Children’s Healthcare Hospital,Gusu School,Nanjing Medical University,Nanjing 211166,China [5]Zhejiang Lab,Hangzhou 311121,China [6]Women’s Hospital,Zhejiang University School of Medicine,Hangzhou 310006,China [7]Shanghai Institute of Stem Cell Research and Clinical Translation,Shanghai 200120,China

出　　处：《National Science Review》2025年第1期37-47,共11页国家科学评论(英文版)

基　　金：supported by the National Key R&D Program of China(2020YFA0113200[Y.G.],2021YFC2700300[S.G.]and 2022YFC2702200[S.G.]);the National Natural Science Foundation of China(32370869[Y.G.],32330030[S.G.],92168205[S.G.],32200694[Y.W],82301859[M.Q.]);Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai(S.G.),Young Elite Scientists Sponsorship Program by CAST(2023QNRC001[Y.W]);the key project of the Science and Technology of Shanghai Municipality(21JC1405500[S.G.]);the Shanghai Rising-Star Program(22YF1436200[Y.W.]);the Shanghai Pilot Program for Basic Research(Y.G.),Special Fund for Health Science and Technology of Social Development Shanghai Pudong New Area(PKJ2022-Y20)(L.C.);Fundamental Research Funds for the Central Universities and the China Postdoctoral Science Foundation(2023M733267[P.Z.]).

摘　　要：The overactivation of transposable elements(TEs)is a significant threat to male reproduction,particularly during the delicate process of spermatogenesis.Here,we report that zinc finger protein ZCCHC8-a key component of the nuclear exosome targeting(NEXT)complex that is involved in ribonucleic acid(RNA)survei l lance-is required for TE silencing during spermatogenesis.Loss of ZCCHC8 results in delayed meiotic progression and reduced production of round spermatids(RS).We observed that young long-interspersed nuclear element(LINE1,L1)subfamilies that are targeted by ZCCHC8 were upregulated in both spermatogonial stem cells(SSC)and pachytene spermatocytes(PS)of Zcchc8 null testes.Further study found that a reduced H3K9me3 modification in SSC and elevated H3 lysine 4 trimethylation in the PS of Zcchc8 KO mice occurred upon young L1,especially L1Md_A,which may have contributed to impairment of the chromatin condensation from PS to RS during spermatogenesis.This study highlights the crucial role of RNA survei l lance-mediated chromatin repression by the NEXT complex during spermatogenesis.

关 键 词：transposon elements nuclear exosome targeting complex LINE1 spermatogonial stem cells SPERMATOGENESIS 

分 类 号：R73[医药卫生—肿瘤]