title: A shared role for RBF1 and dCAP-D3 in the regulation of transcription with consequences for innate immunity.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, The Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. longwom@ccf.org
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Longworth
authors.forename: James A
authors.initials: JA
authors.lastname: Walker
authors.forename: Endre
authors.initials: E
authors.lastname: Anderssen
authors.forename: Nam-Sung
authors.initials: NS
authors.lastname: Moon
authors.forename: Andrew
authors.initials: A
authors.lastname: Gladden
authors.forename: Margarete M S
authors.initials: MM
authors.lastname: Heck
authors.forename: Sridhar
authors.initials: S
authors.lastname: Ramaswamy
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Dyson
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology; D005216:Fat Body / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000235:genetics; D005810:Multigene Family; D009928:Organ Specificity; D010587:Phagocytosis / Q000235:genetics; D059007:Polytene Chromosomes / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity; D016160:Retinoblastoma Protein; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D023181:Antimicrobial Cationic Peptides; C488990:AttA protein, Drosophila; C488991:AttB protein, Drosophila; D029721:Drosophila Proteins; C099965:Rbf protein, Drosophila; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C529732:CAP-D3 protein, Drosophila