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.

作为人类免疫缺陷病毒（HIV）整合的宿主因素，LEDGF / p75已作为治疗的潜在靶点而受到广泛研究。但是，作为高度保守的蛋白质，其生理功能尚待彻底阐明。在这里，我们表征产卵过程中dP75（LEDGF / p75的果蝇同源物）的分子功能。dP75通过其PWWP域与转录活性染色质结合。dP75的C端整合酶结合域含区与组蛋白激酶Jil-1发生物理相互作用并使其在体内稳定。dP75与Jil-1一起可防止异染色质标记-H3K9me2-扩散到卵子发生和piRNA产生所需的基因上。如果没有dP75，这些基因的异位沉默会破坏卵子发生，激活转座子并导致动物不育。我们建议dP75，果蝇中的HIV宿主因子的同源物，与Jil-1结合并使其稳定，以通过防止异位异染色质扩散来确保卵子发生期间的基因表达。