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


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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    • "Drosophila SMRTER (Smr, a relative of SMRT and NCoR) is known to be crucial to ligand-independent repression (Tsai et al. 1999;Sedkov et al. 2003). There is ample evidence that remodeling factors including SWI/SNF and the NURF complex interact with EcR/USP and play key roles in ecdysone response (Badenhorst et al. 2005;Zraly et al. 2006;Ables and Drummond-Barbosa 2010;Kugler et al. 2011;Zraly and Dingwall 2012). There is also evidence that ecdysone induced expression is associated with acetylation of H3K23 (Bodai et al. 2012). "
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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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