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

Institute of Biomedical Research, University of Birmingham, Edgbaston, B15 2TT, UK.
Developmental Biology (Impact Factor: 3.55). 05/2008; 316(2):538-47. DOI: 10.1016/j.ydbio.2008.01.033
Source: PubMed


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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    • "For this analysis, an additional fly line was included that was predicted to over-express the sid gene (hopTum; [26]). The hopTum transgenic fly line that expresses a constitutively active JAK (Janus) kinase, was previously shown to over-express the sid gene by ∼4 fold [26]. While expression of the sid gene was found to be slightly up-regulated (∼1.4 fold; Figure 4A) in hopTum larvae, this gene was highly up-regulated (18.6 fold; Figure 4B) in adult flies. "
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    • "Nevertheless, Pzg can also negatively regulate the expression, as, for example, when it directly binds the co-repressor KEN in the JAK/STAT pathway [14]. The identification of Pzg in a protein complex composed of KEN and NURF in immunoprecipitation experiments, together with the observation of melanotic tumors in pzg mutant flies, which was due to an overexpression of defense response genes, strongly suggested the involvement of Pzg and NURF in the transcriptional repression of the JAK/STAT pathway genes [14,15]. "
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    • "Of the 15 predicted subfamilies that were identified in Drosophila [14], only a handful has been studied in greater detail and even fewer with respect to their role in the immune response of the fly. Two prominent chromatin remodeling factors that have been found to be involved in the regulation of Drosophila defense mechanisms are the nucleosome remodeling factor (NURF) complex and Domino [15]–[17]. NURF, which contains the motor subunit ISWI, was demonstrated to act as a corepressor of STAT target genes, thereby modulating the JAK/STAT-mediated immune response [15], [18], [19]. Domino (Dom), a fly homolog of the yeast and mammalian Swr1 ATPases, has originally been described as a factor required for hemocyte formation [16], [20], [21] and was recently found to control the regulation of a large subset of immunity-related genes [17]. "
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