Splice Variants of the SWR1-type Nucleosome Remodeling Factor Domino Have

24 SWR1-type nucleosome remodeling factors replace histone H2A by variants to endow chromatin lo25 cally with specialized functionality. In Drosophila melanogaster a single H2A variant, H2A.V, com26 bines functions of mammalian H2A.Z and H2A.X in transcription regulation and DNA damage re27 sponse. A major role in H2A.V incorporation for the only SWR1-like enzyme in flies, Domino, is 28 assumed, but not well documented in vivo. It is also unclear, whether the two alternatively spliced 29 isoforms, dom-A and dom-B, have redundant or specialized functions. Loss of both DOM isoforms 30 compromises oogenesis causing female sterility. Therefore, we systematically explored roles of the 31 two DOM isoforms during oogenesis using a cell type-specific knockdown approach. Despite their 32 ubiquitous expression, DOM-A and DOM-B have non-redundant functions in germline and soma for 33 egg chamber formation. We show that chromatin incorporation of H2A.V in germline and somatic 34 cells depends on DOM-B, while incorporation in endoreplicating germline nurse cells is independent 35 of DOM. In contrast, DOM-A promotes the removal of H2A.V from stage 5 nurse cells. Remarkably, 36 the two DOM isoforms have distinct functions in cell type-specific development and H2A.V ex37