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作 者:Kun Dou Yanchao Liu Yingpei Zhang Chenhui Wang Ying Huang ZZ Zhao Zhang
机构地区:[1]Department of Embryology,Carnegie Institution for Science,Baltimore,MD,21218,USA [2]School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China [3]State Key Laboratory of Molecular Biology,Shanghai Key Laboratory of Molecular Andrology,Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,Shanghai 200031,China [4]State Key Laboratory of Oncogenes and Related Genes,Shanghai Key Laboratory of Biliary Tract Disease Research,Shanghai Research Center of Biliary Tract Disease,Department of General Surgery,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200092,China [5]Department of Pharmacology and Cancer Biology,Duke University School of Medicine,Durham,NC,27710,USA [6]Regeneration Next,Duke University,Durham,NC,27710,USA
出 处:《Journal of Genetics and Genomics》2020年第4期187-199,共13页遗传学报(英文版)
基 金:supported by the grant from the NIH to Z.Z.(DP5OD021355);the National Natural Science Foundation of China(91940302 and 31870741 to Y.H.)。
摘 要:Serving as a host factor for human immunodeficiency virus(HIV)integration,LEDGF/p75 has been under extensive study as a potential target for therapy.However,as a highly conserved protein,its physiological function remains to be thoroughly elucidated.Here,we characterize the molecular function of dP75,the Drosophila homolog of LEDGF/p75,during oogenesis.dP75 binds to transcriptionally active chromatin with its PWWP domain.The C-terminus integrase-binding domain-containing region of dP75 physically interacts with the histone kinase Jil-1 and stabilizes it in vivo.Together with Jil-1,dP75 prevents the spreading of the heterochromatin mark-H3 K9 me2-onto genes required for oogenesis and piRNA production.Without dP75,ectopical silencing of these genes disrupts oogenesis,activates transposons,and causes animal sterility.We propose that dP75,the homolog of an HIV host factor in Drosophila,partners with and stabilizes Jil-1 to ensure gene expression during oogenesis by preventing ectopic heterochromatin spreading.
关 键 词:DROSOPHILA LEDGF/p75 Jil-1 H3K9me2
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