A shared role for RBF1 and dCAP-D3 in the regulation of transcription with consequences for innate immunity

PLoS Genet. 2012;8(4):e1002618. doi: 10.1371/journal.pgen.1002618. Epub 2012 Apr 5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphatases* / genetics
  • Adenosine Triphosphatases* / metabolism
  • Animals
  • Antimicrobial Cationic Peptides* / genetics
  • Antimicrobial Cationic Peptides* / immunology
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster* / genetics
  • Drosophila melanogaster* / immunology
  • Fat Body / cytology
  • Fat Body / metabolism
  • Gene Expression Regulation
  • Immunity, Innate* / genetics
  • Multigene Family
  • Organ Specificity
  • Phagocytosis / genetics
  • Polytene Chromosomes / genetics
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / pathogenicity
  • Retinoblastoma Protein
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / pathogenicity
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism
  • Transcription, Genetic

Substances

  • Antimicrobial Cationic Peptides
  • AttA protein, Drosophila
  • AttB protein, Drosophila
  • Drosophila Proteins
  • Rbf protein, Drosophila
  • Retinoblastoma Protein
  • Transcription Factors
  • Adenosine Triphosphatases
  • CAP-D3 protein, Drosophila