title: The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response.
abstract: The host defense of the model organism Drosophila is under the control of two major signaling cascades controlling transcription factors of the NF-B family, the Toll and the immune deficiency (IMD) pathways. The latter shares extensive similarities with the mammalian TNF-R pathway and was initially discovered for its role in anti-Gram-negative bacterial reactions. A previous interactome study from this laboratory reported that an unexpectedly large number of proteins are binding to the canonical components of the IMD pathway. Here, we focus on DNA methyltransferase-associated protein 1 (DMAP1), which this study identified as an interactant of Relish, a Drosophila transcription factor reminiscent of the mammalian p105 NF-B protein. We show that silencing of DMAP1 expression both in S2 cells and in flies results in a significant reduction of Escherichia coli-induced expression of antimicrobial peptides. Epistatic analysis indicates that DMAP1 acts in parallel or downstream of Relish. Co-immunoprecipitation experiments further reveal that, in addition to Relish, DMAP1 also interacts with Akirin and the Brahma-associated protein 55 kDa (BAP55). Taken together, these results reveal that DMAP1 is a novel nuclear modulator of the IMD pathway, possibly acting at the level of chromatin remodeling.
authors.forename: Akira
authors.initials: A
authors.lastname: Goto
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Fukuyama
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Imler
authors.forename: Jules A
authors.initials: JA
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000276:immunology; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology*; D004331:Drosophila melanogaster; D004843:Epistasis, Genetic / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D009687:Nuclear Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D029721:Drosophila Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C101626:Rel protein, Drosophila; D012097:Repressor Proteins; D014157:Transcription Factors; C526726:akirin protein, Drosophila