Yanchao Liu
Yingpei Zhang
Chenhui Wang
Ying Huang
ZZ Zhao Zhang
aDepartment of Embryology, Carnegie Institution for Science, Baltimore, MD, 21218, USA
bSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
cState 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
dState 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
eDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, 27710, USA
fRegeneration Next, Duke University, Durham, NC, 27710, USA
More InformationCorresponding author: E-mail address: doukun@shanghaitech.edu.cn (Kun Dou);E-mail address: huangying@xinhuamed.com.cn (Ying Huang);E-mail address: z.z@duke.edu (ZZ Zhao Zhang)
Publish Date:2020-04-25
Abstract
Abstract
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-H3K9me2-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.Keywords: LEDGF/p75,
Jil-1,
H3K9me2
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