Drosophila P75 safeguards oogenesis by preventing H3K9me2 spreading

Kun Dou; Yanchao Liu; Yingpei Zhang; Chenhui Wang; Ying Huang; ZZ Zhao Zhang

doi:10.1016/j.jgg.2020.02.008

Volume 47 Issue 4

Apr. 2020

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Article Navigation > Journal of Genetics and Genomics > 2020 > 47(4): 187-199

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Drosophila P75 safeguards oogenesis by preventing H3K9me2 spreading

doi: 10.1016/j.jgg.2020.02.008

Kun Dou^{a, b},
Yanchao Liu^{c, 1},
Yingpei Zhang^{c, 1},
Chenhui Wang^a,
Ying Huang^{c, d},
ZZ Zhao Zhang^{a, e, f}

a
Department of Embryology, Carnegie Institution for Science, Baltimore, MD, 21218, USA
b
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
c
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
d
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
e
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, 27710, USA
f
Regeneration Next, Duke University, Durham, NC, 27710, USA

More Information

Corresponding 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.
- LEDGF/p75,
- Jil-1,
- H3K9me2

These authors contributed equally to this work.

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References(41)

References

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