dP75 safeguards oogenesis by preventing H3K9me2 spreading

Serving as a host factor for 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 homolog of p75, during oogenesis. dP75 binds to transcriptionally active chromatin with its PWWP domain. The C-terminus IBD domain-containing region of dP75 physically interacts with the histone kinase Jil-1 and stabilizes it . Together with Jil-1, dP75 prevents the spreading of the heterochromatin mark–H3K9me2–onto genes required for oogenesis and piRNA production. Without dP75, ectopically silencing of these genes disrupts oogenesis, activates transposons, and causes animal sterility. We propose that dP75, the homolog of an HIV host factor in , partners with Jil-1 to ensure gene expression during oogenesis by preventing ectopic heterochromatin spreading.