DEAF-1 regulates immunity gene expression in Drosophila

Darien E. Reed, Xinhua M. Huang, James A. Wohlschlegel, Michael S. Levine, Kate Senger

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Immunity genes are activated in the Drosophila fat body by Rel and GATA transcription factors. Here, we present evidence that an additional regulatory factor, deformed epidermal autoregulatory factor-1 (DEAF-1), also contributes to the immune response and is specifically important for the induction of two genes encoding antimicrobial peptides, Metchnikowin (Mtk) and Drosomycin (Drs). The systematic mutagenesis of a minimal Mtk 5′ enhancer identified a sequence motif essential for both a response to LPS preparations in S2 cells and activation in the larval fat body in response to bacterial infection. Using affinity chromatography coupled to multidimensional protein identification technology (MudPIT), we identified DEAF-1 as a candidate regulator. DEAF-1 activates the expression of Mtk and Drs promoter-luciferase fusion genes in S2 cells. SELEX assays and footprinting data indicate that DEAF-1 binds to and activates Mtk and Drs regulatory DNAs via a TTCGGBT motif. The insertion of this motif into the Diptericin (Dpt) regulatory region confers DEAF-1 responsiveness to this normally DEAF-1-independent enhancer. The coexpression of DEAF-1 with Dorsal, Dif, and Relish results in the synergistic activation of transcription. We propose that DEAF-1 is a regulator of Drosophila immunity.

Original languageEnglish (US)
Pages (from-to)8351-8356
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number24
DOIs
StatePublished - Jun 17 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Drosomycin
  • Metchnikowin
  • MudPIT
  • Transcription

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