Previously, we discovered a conserved interaction between RB proteins and the Condensin II protein CAP-D3 that is important for ensuring uniform chromatin condensation during mitotic prophase. The Drosophila melanogaster homologs RBF1 and dCAP-D3 co-localize on non-dividing polytene chromatin, suggesting the existence of a shared, non-mitotic role for these two proteins. Here, we show that the absence of RBF1 and dCAP-D3 alters the expression of many of the same genes in larvae and adult flies. Strikingly, most of the genes affected by the loss of RBF1 and dCAP-D3 are not classic cell cycle genes but are developmentally regulated genes with tissue-specific functions and these genes tend to be located in gene clusters. Our data reveal that RBF1 and dCAP-D3 are needed in fat body cells to activate transcription of clusters of antimicrobial peptide (AMP) genes. AMPs are important for innate immunity, and loss of either dCAP-D3 or RBF1 regulation results in a decrease in the ability to clear bacteria. Interestingly, in the adult fat body, RBF1 and dCAP-D3 bind to regions flanking an AMP gene cluster both prior to and following bacterial infection. These results describe a novel, non-mitotic role for the RBF1 and dCAP-D3 proteins in activation of the Drosophila immune system and suggest dCAP-D3 has an important role at specific subsets of RBF1-dependent genes. Author Summary The retinoblastoma protein (pRB) is a tumor suppressor protein known for its ability to repress transcription of E2F-dependent genes and induce cell cycle arrest. We have previously shown that RB proteins in Drosophila and human cells interact with the Condensin II subunit, CAP-D3, in an E2F-independent manner. Condensins promote condensation of chomosomes in mitosis. Our previous studies suggested that the Drosophila pRB and CAP-D3 homologs, RBF1 and dCAP-D3, co-localize on DNA and may share a function in cells that never undergo mitosis. In this study, we show that one non-mitotic function shared between RBF1 and dCAP-D3 is the regulation of many non-cell-cycle-related, clustered, and cell-type-specific transcripts including a conserved family of genes that are important for the immune response in the fly. In fact, results show that normal levels of dCAP-D3 and RBF1 expression are necessary for the ability of the fly to clear infection with human bacterial pathogens. This work demonstrates that dCAP-D3 proteins can regulate a unique subset of RBF1-dependent transcripts in vivo and identifies a novel role for both RBF1 and dCAP-D3 protein in activation of innate immune genes, which may be conserved in human cells.
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