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Contenuto archiviato il 2024-05-30

Regulatory Genomics in Drosophila

Final Report Summary - REGULATORY GENOMICS (Regulatory Genomics in Drosophila)

Animal genomes encode all proteins and the information about their expression during development. While we have a detailed understanding of the genetic code that describes the encoding of proteins, we are lacking knowledge about the sequence required for gene regulation, i.e. a regulatory code (Yanez-Cuna et al., Trends in Genetics, 2012).

The project ‘Regulatory Genomics’ (242922) combined the genome-wide experimental characterization of regulatory sequences with their computational analysis. We have established computational tools to compare the in vivo binding of transcription factors (regulatory proteins; TFs) to specific regions in the genome and to extract sequence features that are predictive of TF binding (Yanez-Cuna et al., Genome Research 2012). We have further characterized enhancer candidates functionally in vivo (Kvon et al., Genes & Development 2012; Kvon et al., Nature 2014) and in cell culture. For the latter, we have established a novel method, STARR-seq, which allows the genome-wide assessment of enhancer strengths (Arnold et al., Science 2013). This method allowed us to study enhancers active in different cells (Yanez-Cuna et al., Genome Research 2014), hormone-responsive enhancers (Shlyueva et al., Molecular Cell 2014), the evolution of enhancer activity across the Drosophila phylogeny (Arnold et al., Nature Genetics 2014), and to describe two different types of enhancers that activate transcription from housekeeping and developmental core promoters, respectively (Zabidi et al., Nature 2015).