The nucleosome remodeling factor (NURF) regulates genes involved in Drosophila innate immunity

Institute of Biomedical Research, University of Birmingham, Edgbaston, B15 2TT, UK.
Developmental Biology (Impact Factor: 3.64). 05/2008; 316(2):538-47. DOI: 10.1016/j.ydbio.2008.01.033
Source: PubMed

ABSTRACT The Drosophila nucleosome remodeling factor (NURF) is an ISWI-containing chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding. By sliding nucleosomes, NURF has the ability to alter chromatin structure and regulate transcription. Previous studies have shown that mutation of Drosophila NURF induces melanotic tumors, implicating NURF in innate immune function. Here, we show that NURF mutants exhibit identical innate immune responses to gain-of-function mutants in the Drosophila JAK/STAT pathway. Using microarrays, we identify a common set of target genes that are activated in both mutants. In silico analysis of promoter sequences of these defines a consensus regulatory element comprising a STAT-binding sequence overlapped by a binding-site for the transcriptional repressor Ken. NURF interacts physically and genetically with Ken. Chromatin immunoprecipitation (ChIP) localizes NURF to Ken-binding sites in hemocytes, suggesting that Ken recruits NURF to repress STAT responders. Loss of NURF leads to precocious activation of STAT target genes.

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Available from: Paul Badenhorst, Mar 17, 2014
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    • "We examine the biochemical, structural, and functional properties endowed by a bivalent configuration of these linked effector domains, the simplest case of multivalent histone modification-dependent nucleosomal engagement (Ruthenburg et al., 2007b). BPTF in the context of the NURF complex is an essential regulator of chromatin structure in development (Badenhorst et al., 2002; Landry et al., 2008; Wysocka et al., 2006), bringing about transcriptional activation or repression in a locus-specific manner (Bai et al., 2007; Kwon et al., 2008) by virtue of the complex's chromatin remodeling activity (Hamiche et al., 1999; Tsukiyama and Wu, 1995). The second PHD finger of BPTF, implicated in recruitment or stabilization of the NURF complex to active homeotic genes as a consequence of MLL1-mediated H3K4 trimethylation, is followed closely by a bromodomain whose mechanistic role is obscure (Wysocka et al., 2006). "
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    • "Although we have not characterized dei's expression in all developmental stages and tissues, published data of various microarray analyses suggest that dei is expressed in other developmental and physiological contexts where up-regulation of βPS integrin is required. For example, dei was up-regulated when larvae were exposed to immune challenge, or when mutant larvae exhibited an increase in lamellocyte cell population (Irving et al., 2005; Kwon et al., 2008). Lamellocytes represent a subset of hemocytes in Drosophila, which differentiate in response to specific immune challenge. "
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    • "Here, we provide the molecular evidence to show that Pzg, with NURF, acts as a corepressor of Ken with respect to STAT responsive genes, thereby preventing an immune-mediated inflammatory syndrome, i.e., melanotic tumor formation. The Pzg protein physically interacts with Ken and is present at STAT responsive promoters, as well as at the promoter of a gene (CG5791) that is bound by both Ken and NURF alike (Kwon et al. 2008). In an attempt to visualize increased JAK/STAT activity, particularly in hemocytes, we tried to monitor the expression of the STAT92E–GFP reporter in a hop Tum-l -sensitized background; however, we failed to detect a specific activity, which went beyond the normal background staining in the wild type (data not shown). "
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