Transcriptional Regulation by CHIP/LDB Complexes

Abstract

It is increasingly clear that transcription factors play versatile roles in turning genes “on” or “off” depending on cellular context via the various transcription complexes they form. This poses a major challenge in unraveling combinatorial transcription complex codes. Here we use the powerful genetics of Drosophila combined with microarray and bioinformatics analyses to tackle this challenge. The nuclear adaptor CHIP/LDB is a major developmental regulator capable of forming tissue-specific transcription complexes with various types of transcription factors and cofactors, making it a valuable model to study the intricacies of gene regulation. To date only few CHIP/LDB complexes target genes have been identified, and possible tissue-dependent crosstalk between these complexes has not been rigorously explored. SSDP proteins protect CHIP/LDB complexes from proteasome dependent degradation and are rate-limiting cofactors for these complexes. By using mutations in SSDP, we identified 189 down-stream targets of CHIP/LDB and show that these genes are enriched for the binding sites of APTEROUS (AP) and PANNIER (PNR), two well studied transcription factors associated with CHIP/LDB complexes. We performed extensive genetic screens and identified target genes that genetically interact with components of CHIP/LDB complexes in directing the development of the wings (28 genes) and thoracic bristles (23 genes). Moreover, by in vivo RNAi silencing we uncovered novel roles for two of the target genes, xbp1 and Gs-alpha, in early development of these structures. Taken together, our results suggest that loss of SSDP disrupts the normal balance between the CHIP-AP and the CHIP-PNR transcription complexes, resulting in down-regulation of CHIP-AP target genes and the concomitant up-regulation of CHIP-PNR target genes. Understanding the combinatorial nature of transcription complexes as presented here is crucial to the study of transcription regulation of gene batteries required for development.

Modularity of CHIP/LDB transcription complexes regulates cell differentiation

“…Yet, no extra bristles were observed on the scutellum, and some of these flies even exhibited a reduced number of scutellar bristles. 23 these observations indicate that the function of Xbp1 depends on differences between the cellular milieu of the scutum and scutellum. these differences apparently extend beyond the transcription regulation of the CHIP-aP and CHIP-Pnr complexes, allowing for further specificity in directing the differentiation of these tissues.…”

“…In a recent study, 23 we aimed at analyzing the effect of changing the repertoire of transcription co-factors on the function of two competing transcription complexes that are highly conserved from flies to mice. Both complexes assemble via the co-factor CHIP/LDB (alias CLIM or nLI).…”

“…64 the binding sites for both KnI and sn were enriched in the upstream regulatory regions of putative target genes in our study. 23 Moreover, CtBP can directly bind Pnr and its FoG co-repressor protein u-shaped (usH). this interaction negatively regulates the Pnr-mediated proneural activation of ac/sc during thoracic sensory organ patterning.…”

SEUSS Integrates Gibberellin Signaling with Transcriptional Inputs from the SHR-SCR-SCL3 Module to Regulate Middle Cortex Formation in the Arabidopsis Root

“…SEUSS (SEU) encodes an Arabidopsis protein with a conserved central domain that shares sequence homology with the dimerization domain of the LIMdomain-binding transcriptional coregulators (Franks et al, 2002), which play fundamental roles in animal development (Matthews and Visvader, 2003;Bronstein et al, 2010;Bronstein and Segal, 2011). SEU is widely expressed in Arabidopsis and functions in many developmental processes, including floral organ identity specification, gynoecium, ovule and embryo development, and lateral root initiation (Franks et al, 2002;Pfluger and Zambryski, 2004;Sridhar et al, 2006; .…”

Transcriptional activators and activation mechanisms

“…For example, the Drosophila protein called Chip, which can interact with many transcription factors and co-factors (Morcillo et al, 1997;Torigoi et al, 2000;Matthews and Visvader, 2003;Bronstein et al, 2010), has been proposed to play such a role (Dorsett, 1999). In addition, recent studies have revealed critical roles of cohesin and noncoding RNAs in facilitating the communication between enhancers and promoters (Ong and Corces, 2011).…”