Splice Variants of the SWR1-type Nucleosome Remodeling Factor Domino Have Distinct Functions during Drosophila melanogaster Oogenesis

Abstract

SWR1-type nucleosome remodeling factors replace histone H2A by variants to endow chromatin locally with specialized functionality. In Drosophila melanogaster a single H2A variant, H2A.V, combines functions of mammalian H2A.Z and H2A.X in transcription regulation and DNA damage response. A major role in H2A.V incorporation for the only SWR1-like enzyme in flies, Domino, is assumed, but not well documented in vivo. It is also unclear, whether the two alternatively spliced isoforms, dom-A and dom-B, have redundant or specialized functions. Loss of both DOM isoforms compromises oogenesis causing female sterility. Therefore, we systematically explored roles of the two DOM isoforms during oogenesis using a cell type-specific knockdown approach. Despite their ubiquitous expression, DOM-A and DOM-B have non-redundant functions in germline and soma for egg chamber formation. We show that chromatin incorporation of H2A.V in germline and somatic cells depends on DOM-B, while incorporation in endoreplicating germline nurse cells is independent of DOM. In contrast, DOM-A promotes the removal of H2A.V from stage 5 nurse cells. Remarkably, the two DOM isoforms have distinct functions in cell type-specific development and H2A.V exchange.\n\nSummary Statement\n\nIsoforms of nucleosome remodeling factor Domino change chromatin structure by histone variant exchange to direct essential cellular processes in oocyte development.