The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response

Akira Tajima-Goto (1, 2) , Hidehiro Fukuyama (1, 2) , Jean-Luc Imler (1, 2) , Jules Hoffmann (1, 2)

1 RIDI - UPR 9002 - Réponse immunitaire et developpement chez les insectes
2 M3I - Modèles Insectes de l'Immunité Innée

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.

Domains: Immunology

Akira Tajima-Goto, Hidehiro Fukuyama, Jean-Luc Imler, Jules Hoffmann. The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response. Journal of Biological Chemistry, 2014, 289 (30), pp.20470-20476. ⟨10.1074/jbc.C114.553719⟩. ⟨hal-02310183⟩