The insulator protein Suppressor of Hairy-wing is an essential transcriptional repressor in theDrosophilaovary

Abstract

SUMMARYSuppressor of Hairy-wing [Su(Hw)] is a DNA-binding factor required for gypsy insulator function and female germline development in Drosophila. The insulator function of the gypsy retrotransposon depends on Su(Hw) binding to clustered Su(Hw) binding sites (SBSs) and recruitment of the insulator proteins Centrosomal Protein 190 kD (CP190) and Modifier of mdg4 67.2 kD (Mod67.2). By contrast, the Su(Hw) germline function involves binding to non-clustered SBSs and does not require CP190 or Mod67.2. Here, we identify Su(Hw) target genes, using genome-wide analyses in the ovary to uncover genes with an ovary-bound SBS that are misregulated upon Su(Hw) loss. Most Su(Hw) target genes demonstrate enriched expression in the wild-type CNS. Loss of Su(Hw) leads to increased expression of these CNS-enriched target genes in the ovary and other tissues, suggesting that Su(Hw) is a repressor of neural genes in non-neural tissues. Among the Su(Hw) target genes is RNA-binding protein 9 (Rbp9), a member of the ELAV/Hu gene family. Su(Hw) regulation of Rbp9 appears to be insulator independent, as Rbp9 expression is unchanged in a genetic background that compromises the functions of the CP190 and Mod67.2 insulator proteins, even though both localize to Rbp9 SBSs.

Two new insulator proteins, Pita and ZIPIC, target CP190 to chromatin

“…Binding sites for dCTCF have been identified in the insulators that separate functional regulatory domains of the bithorax complex and in many promoter regions (Moon et al 2005;Holohan et al 2007;Mohan et al 2007;N egre et al 2010Ni et al 2012). The Su(Hw) protein more frequently associates with intergenic sites Bushey et al 2009;N egre et al 2010Soshnev et al 2012Soshnev et al , 2013. As shown in a transgenic assay, dCTCF and Su(Hw) binding sites can support specific distant interactions (Kyrchanova et al 2008a,b), which suggests a key role for these proteins in organizing chromatin architecture.…”

Distinct Roles of Chromatin Insulator Proteins in Control of the Drosophila Bithorax Complex

“…It seems that the main function of Mod(mdg4)67.2 at the gypsy insulator is to prevent the associated Su(Hw) protein from acting as transcriptional repressor (Gerasimova et al 1995;Georgiev and Kozycina 1996). Consistently, genomic sites that bind Su(Hw) protein in the absence of Mod(mdg4)67.2 act as repressive elements (Schwartz et al 2012;Soshnev et al 2013). mod(mdg4) is a complex gene that encodes 30 protein isoforms through a trans-splicing of pre-mRNAs produced from both DNA strands (Dorn et al the Abd-B gene is reduced and that A5 is partially transformed into A4 (Dorn et al 1993;Buchner et al 2000).…”

The BEAF-32 insulator protein is required for Hippo pathway activity in the terminal differentiation of neuronal subtypes

“…This definition has expanded to include proteins that mediate chromosomal interactions to regulate 3D chromatin organization and global gene expression (Bushey et al, 2009;Phillips-Cremins and Corces, 2013;Wood et al, 2011). Despite these studies, surprisingly few roles for insulator proteins in specific biological processes in flies have been characterized, including the regulation of oogenesis (Hsu et al, 2015;Roy et al, 2007;Soshnev et al, 2013) and spermatogenesis (Soltani-Bejnood et al, 2007;Thomas et al, 2005). Our result that BEAF regulates Hippo pathway activity for terminal differentiation of R8 neuronal subtypes, but has no observed effect on general growth control or other photoreceptor fate, indicates that broadly expressed insulators can have exquisitely specific functions in development.…”