IRTG2403 - Regulatory Genome

High-throughput technologies to dissect and perturb regulatory mechanisms at genomic scale

With the advent of genome wide sequencing approaches, it has been possible to map the linear genomic information from a variety of organisms. The development of chromatin immunoprecipitation helped to identify molecular signatures of biological function across the genome and, importantly, how these signatures vary across cell types and organs. As technologies improve, we have obtained an increasingly fine-scaled understanding of genomic function with the inclusion of new features such as nucleosome positioning and ‘open’ chromatin states permissive to regulation through the binding of specific transcription factors. Deep transcriptome sequencing has expanded our view of RNA from coding messenger RNA to include nascent transcripts and non-coding RNAs, including transcription at enhancers (eRNA) and long, non-coding RNA molecules that have structural and regulatory functions which we are only beginning to understand. How different transcription events are regulated remains unexplored. Lastly, technologies that map chromatin 3D topology show the importance of 3D interactions for gene regulation at multiple scales. While high-throughput methods allow for extensive characterization of regulatory landscapes, our ability to infer causal relationships from high-throughput data requires advanced computational approaches that can incorporate and infer the inherent heterogeneity of cells and regulatory mechanisms. Improved technologies for perturbing and dissecting complex regulatory networks are also essential and are the focus of four projects in this proposal, two aimed at fine-scale perturbations of regulatory processes and two aimed at single-cell approaches for tissues and organisms comprised of cells defined by distinct regulatory states. Projects will provide students with skills that go beyond descriptive regulatory profiling to the dissection and manipulation of gene expression regulation in complex tissues.


Involed research groups: