The Putzig-NURF Nucleosome Remodeling Complex Is Required for Ecdysone Receptor Signaling and Innate Immunity in Drosophila melanogaster

Institute of Genetics, University of Hohenheim, Stuttgart, Germany.
Genetics (Impact Factor: 5.96). 03/2011; 188(1):127-39. DOI: 10.1534/genetics.111.127795
Source: PubMed

ABSTRACT Putzig (Pzg) was originally identified as being an integral component of the TRF2/DREF complex in Drosophila melanogaster, thereby regulating the transcriptional activation of replication-related genes. In a DREF-independent manner, Pzg was shown to mediate Notch target gene activation. This function of Pzg entails an association with the nucleosome remodeling factor complex NURF, which directly binds the ecdysone receptor EcR and coregulates targets of the EcR via the NURF-specific subunit Nurf-301. In contrast, Nurf-301 acts as a negative regulator of JAK/STAT signaling. Here, we provide evidence to show that Pzg is fundamental for these functions of NURF, apart from the regulation of Notch signaling activity. A jump-out mutagenesis provided us with a pzg null mutant displaying early larval lethality, defects in growth, and molting accompanied by aberrant feeding behavior. We show that Pzg is associated with EcR in vivo and required for the transcriptional induction of EcR target genes, whereas reduced ecdysteroid levels imply a NURF-independent function of Pzg. Moreover, pzg interferes with JAK/STAT-signaling activity by acting as a corepressor of Ken. Lamellocyte differentiation was consistently affected in a JAK/STAT mutant background and the expression level of defense response genes was elevated in pzg mutants, leading to the formation of melanotic tumors. Our results suggest that Pzg acts as an important partner of NURF in the regulation of EcR and JAK/STAT signaling.

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    • "The DREF homo-dimer binds specifically to the DRE sequence and, together with TRF2, is required for the cellular shift from the resting state into the proliferating state [13]. 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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    ABSTRACT: Telomere maintenance in Drosophila relies on the targeted transposition of three very special non-LTR retrotransposons, HeT-A, TART, and TAHRE (HTT). The sequences of the retrotransposon array build up the telomere chromatin in this organism. We have recently reported the role of the chromosomal protein Putzig/Z4 in maintaining a proper chromatin structure at the telomere domain of Drosophila. Because the Putzig protein has been found in different cellular complexes related with cell proliferation, development, and immunity, we decided to investigate whether the previously described Putzig partners, DREF/TRF2 and KEN, could also be involved in the telomere function in this organism. We have found that mutant alleles for Dref/Trf2 and Ken show alterations in HeT-A and TART expression, suggesting a possible role of these protein complexes in the regulation of the telomere retrotransposons. In agreement, both HeT-A and TART contain the specific DNA binding sequences for the DREF and the KEN protein proteins. We have identified three new negative regulators involved in the control of the expression of the telomeric retrotransposons, Dref, Trf2, and Ken. Our results offer some clues on which other chromatin-related proteins might be involved in telomere regulation and retrotransposon control.
    Mobile DNA 07/2013; 4(1):18. DOI:10.1186/1759-8753-4-18 · 2.11 Impact Factor
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    • "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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    ABSTRACT: Drosophila SNF2-type ATPase CHD1 catalyzes the assembly and remodeling of nucleosomal arrays in vitro and is involved in H3.3 incorporation in viin vivo during early embryo development. Evidence for a role as transcriptional regulator comes from its colocalization with elongating RNA polymerase II as well as from studies of fly Hsp70 transcription. Here we used microarray analysis to identify target genes of CHD1. We found a fraction of genes that were misregulated in Chd1 mutants to be functionally linked to Drosophila immune and stress response. Infection experiments using different microbial species revealed defects in host defense in Chd1-deficient adults upon oral infection with P. aeruginosa but not upon septic injury, suggesting a so far unrecognized role for CHD1 in intestinal immunity. Further molecular analysis showed that gut-specific transcription of antimicrobial peptide genes was overactivated in the absence of infection in Chd1 mutant flies. Moreover, microbial colonization of the intestine was elevated in Chd1 mutants and oral infection resulted in strong enrichment of bacteria in the body cavity indicating increased microbial passage across intestinal epithelia. However, we did not detect enhanced epithelial damage or alterations of the intestinal stem cell population. Collectively, our data provide evidence that intestinal resistance against infection by P. aeruginosa in Drosophila is linked to maintaining proper balance of gut-microbe interactions and that the chromatin remodeler CHD1 is involved in regulating this aspect.
    PLoS ONE 08/2012; 7(8):e43144. DOI:10.1371/journal.pone.0043144 · 3.23 Impact Factor
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    • "In addition, in the fly's ovary, ecdysone interacts with chromatin remodeling factors for modulating the proliferation and self-renewal of germline stem cells (Ables and Drummond-Barbosa, 2010). Ecdysone receptor signaling also needs direct cooperation with nucleosome remodeling complexes, and many EcR co-activators and co-repressors that contribute to the epigenetic memory have been identified and characterized (Kimura et al., 2008; Sawatsubashi et al., 2010; Kugler et al., 2011). "
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    ABSTRACT: Wolbachia pipientis is a widespread endosymbiont of filarial nematodes and arthropods. While in worms the symbiosis is obligate, in arthropods Wolbachia induces several reproductive manipulations (i.e., cytoplasmic incompatibility, parthenogenesis, feminization of genetic males, and male-killing) in order to increase the number of infected females. These various phenotypic effects may be linked to differences in host physiology, and in particular to endocrine-related processes governing growth, development, and reproduction. Indeed, a number of evidences links Wolbachia symbiosis to insulin and ecdysteroid signaling, two multilayered pathways known to work antagonistically, jointly or even independently for the regulation of different molecular networks. At present it is not clear whether Wolbachia manipulates one pathway, thus affecting other related metabolic networks, or if it targets both pathways, even interacting at several points in each of them. Interestingly, in view of the interplay between hormone signaling and epigenetic machinery, a direct influence of the "infection" on hormonal signaling involving ecdysteroids might be achievable through the manipulation of the host's epigenetic pathways.
    Frontiers in Endocrinology 01/2011; 2:115. DOI:10.3389/fendo.2011.00115
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