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Departmental Seminar - Alexander Stark : Decoding transcriptional regulation

When Feb 09, 2017
from 02:00 PM to 03:00 PM
Where Biffen Lecture Theatre, underneath Dept of Genetics
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9th February 2017 - Biffen Lecture Theatre

Title: Decoding transcriptional regulation

Dr Alexander Stark, Research Institute of Molecular Pathology, Vienna

Host: Alexis Braun

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. Each cell is able to read the regulatory information in promoter- and enhancer sequences to express specific sets of genes. In contrast, we cannot decipher this regulatory code – a large knowledge gap compared to our detailed understanding of the genetic code, which allows us to seamlessly translate DNA into protein sequences and to determine the protein-coding gene content of any newly sequenced genome.

I am presenting our work towards understanding the regulatory code in Drosophila by an interdisciplinary approach. We functionally characterize regulatory sequences by enhancer screens in Drosophila embryos and cell-culture and by assessing core promoter activities of large candidate libraries. Computational motif analyses coupled to supervised machine-learning methods are powerful tools that allow us to determine motifs that are shared in functionally related sequences and are promising candidates to explain regulatory function. We also study how enhancers activate different types of core promoters and how enhancer – core-promoter specificity is encoded in the two elements’ sequences. We finally 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 and cofactors.