Functions of Transcriptional Co-regulators in Drosophila development

Abstract: During Drosophila development, regulation of gene expression through interplay between transcriptional activators and repressors is generating complex patterns of gene expression that leads to cell differentiation. For proper control of transcription, transcription factors bind to DNA at control regions, so called Cis Regulatory Modules (CRM). Transcription factors recruit additional factors, co-regulators, that affect gene expression through interactions with the general transcription machinery, as well as affect the chromatin environment through post-translational modifications of the histone tails. In this thesis the role of transcriptional co-regulators in Drosophila development is investigated.This work has demonstrated the need for the transcriptional co-activator CREB binding protein (CBP) in signalling by the Transforming Growth Factor-? (TGF-?) molecules Decapentaplegic (Dpp) and Screw (Scw) in early embryos. Furthermore it is shown that the acetyl transferase activity of CBP is dispensable for this function.In a screen for novel regulators of gene expression in the embryo, Brakeless (Bks) was isolated as a co-repressor for the Tailless (Tll) transcription factor. This work shows that Tll function is impaired in bks mutants, that Bks and Tll bind each other in vitro and interact genetically. Bks is present on CRMs controlled by Tll and can repress transcription when tethered to DNA. Bks interacts and functions together with another co-repressor Atrophin.Reptin is part of several complexes including the TIP60 Histone Acetyl Transferase (HAT) complex. Work in this thesis show that Reptin and other members of the TIP60 complex function in formation of silent chromatin in Drosophila.Together these results show that transcriptional co-regulators function selectively in specific processes during development.