GSE112708
ZNFX-1 Functions Within Perinuclear Nuage to Balance Epigenetic Signals
Animal cells have a remarkable capacity to adopt durable and heritable gene expression programs or epigenetic states that define the physical properties and diversity of somatic cell types. The maintenance of epigenetic programs depends on poorly understood pathways that prevent gain or loss of inherited signals. In the germline, epigenetic factors are enriched in liquid-like perinuclear condensates called nuage. Here we identify the deeply conserved helicase-domain protein, ZNFX-1, as an epigenetic regulator and component of nuage that interacts with Argonaute systems to balance epigenetic inheritance. Our findings suggest that ZNFX-1 promotes the 3' recruitment of machinery that propagates the small RNA epigenetic signal and thus counteracts a tendency for Argonaute-targeting to shift 5' along the mRNA.  These functional insights support the idea that recently identified subdomains of nuage, including ZNFX-1 granules or “Z-granules,” may define spatial and temporal zones of molecular activity during epigenetic regulation. Overall design: Small RNA bound to WAGO-9 or CSR-1, as well as total small RNA, from wildtype or znfx-1 mutant animals were cloned in triplicates and sequenced. Please note that both IPs were done using anti-flag mouse monoclonal antibody M2 from Sigma (Cat#F1804) since both CSR-1 and WAGO-9 were tagged with FLAG peptide.