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

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.

Identification of 20-Hydroxyecdysone-Inducible Genes from Larval Brain of the Silkworm, Bombyx mori, and Their Expression Analysis

“…Disruption of the components in PTTH and EcR signaling pathways can cause abnormal development in insects (Gu et al, 2011;Kugler et al, 2011), but it is still unknown how these are correlated with each other at the molecular level. In the present study, we performed a comprehensive screening of genes induced by 20E using DNA microarray …”

JAK/STAT pathway dysregulation in tumors: A Drosophila perspective

“…More recent work has revealed that Putzig (Pzg), a component of the TRF2/DREF replication complex, acts in concert with Nurf301 and Ken to repress JAK/STAT target genes (Fig. 3B and (Kugler et al, 2011)). In support of this model, loss of one copy of Nurf301 , ken or pzg singly or in combination significantly increases the hop Tum-l tumor incidence (Kwon et al, 2008; Kugler et al, 2011).…”

Dissection of open chromatin domain formation by site specific recombination inDrosophila

“…The chromatin-decondensing function of H3S10 phosphorylation, driven by Jil-1, is one possible mechanism for open chromatin formation, as described above. The Z4/Ptz subunit of the Chriz complex has also been suggested to cooperate with the nucleosome-remodeling factor complex NURF (Kugler et al, 2011) to support open chromatin formation. The whole region is depleted for inactive chromatin marks, like H3K9 and H3K27 trimethylation, and enriched for histone modifications typically found in active chromatin, like histone acetylation and H3K4 trimethylation.…”