Decoding Transcriptional Regulation in Drosophila
11 April 2019
Prof. Alexander Stark
Research Institute of Molecular Pathology, Austria
Our aim is to understand how transcription is regulated at the level of the two key types of regulatory genomic elements – enhancers and core-promoters – and the transcription factor and cofactor proteins that mediate transcription activation.
To reach this goal, we follow an interdisciplinary approach, using genome-wide functional assays, bioinformatics, biochemistry, and mass-spectrometry. We develop and employ highly-controllable reporter assays that provide reliable functional readouts for each of the questions we ask, while circumventing the many confounding issues that exist in complex gene regulatory systems in vivo.
See more information at the webpage of Prof. Stark´s group.
About the lecture
In higher eukaryotes, genes are expressed dynamically in complex spatial and temporal patterns, which are progressively refined to set up body plans and define specific cell-types. The information about when and where each gene is to be expressed is encoded in the sequences of promoter- and enhancer regions and realized by transcription factor and cofactor proteins.
I am presenting our work towards understanding the how this regulatory information is sequence-encoded and how cells utilize this information with transcription factor and cofactor proteins. Using an interdisciplinary approach in Drosophila, we functionally characterize regulatory sequences by enhancer screens and by assessing core promoter activities of large candidate libraries. We dissect the combinatorics of transcription factors and transcriptional cofactors at enhancers by directed tethering in enhancer complementation assays, which revealed functionally distinct classes of transcription factors. Finally, we also study how enhancers and the cofactor proteins they recruit activate different types of core promoters, enabling distinct sets of genes and alternative promoters of the same genes to be regulated differently. The distinct compatibilities between cofactors and core promoters forms the basis of specificity within and between gene regulatory programs.