Interactions between Chip and the Achaete/Scute–Daughterless Heterodimers Are Required for Pannier-Driven Proneural Patterning

Abstract

The GATA factor Pannier activates the achaete-scute (ASC) proneural complex through enhancer binding and provides positional information for sensory bristle patterning in Drosophila. Chip was previously identified as a cofactor of the dorsal selector Apterous, and we show here that both Apterous and Chip also regulate ASC expression. Chip cooperates with Pannier in bridging the GATA factor with the HLH Ac/Sc and Daughterless proteins to allow enhancer-promoter interactions, leading to activation of the proneural genes, whereas Apterous antagonizes Pannier function. Within the Pannier domain of expression, Pannier and Apterous may compete for binding to their common Chip cofactor, and the accurate stoichiometry between these three proteins is essential for both proneural prepattern and compartmentalization of the thorax.

Enhancer-bound LDB1 regulates a corticotrope promoter-pausing repression program

“…Mass spectrometry analysis detected LDB1 peptides ( Fig. 2A), consistent with biochemical and genetic interactions of Achaete/Scute and Chip in Drosophila (19). We therefore were interested in determining whether LDB1 was involved in ASCL1 function in the POMC lineage.…”

“…CHIP has been reported to interact with Drosophila proneuronal ASC-Da bHLH factor (19). Our proteomic studies demonstrate that LDB1 interacts strongly with pan bHLH factors, the E-proteins.…”

“…Ascl1 also is expressed in the developing pituitary gland (8), and experiments in Zebrafish suggest its importance during early adenohypophysis development (18). Studies in Drosophila indicate that achaete recruits and functionally requires a cofactor, CHIP, to regulate target genes (19). Lim domain-binding (LDB)/nuclear LIM interactor (NLI)/ cofactor of LIM homeodomain protein (CLIM), the mammalian homolog of CHIP, has been demonstrated to be a critical factor for multiple developmental systems and to be a component of LIM homeodomain codes that determine neuronal subtype specification in the spinal cord (3,20,21).…”

Modularity of CHIP/LDB transcription complexes regulates cell differentiation

“…1) together with an additional co-factor dLMo (Drosophila LIM-only), a Gata family transcription factor, PanIer (Pnr) and the β-HLH transcription factors aCHaete (aC), sCute (sC) and DauGHterLess (Da). [30][31][32] We refer to this second complex as CHIP-Pnr. the two complexes are mutually exclusive.…”

“…1). 30 multiple combinations of tFs. Different combinations (or complexes) direct the specificity of CrM binding and target genes selection and can even determine activation or repression mode of operation.…”