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3D Organization of Functionally Conserved Cis-Regulatory Elements


Embryonic development requires precise spatio-temporal gene expression generating numerous cell types that build the animal body plan. Cell-fate specification and patterning are driven by developmental genes that are often expressed in complex and conserved fashion. Gene expression is precisely modulated by gene regulatory networks (GRNs) constructed through the integration of signalling pathways acting at cis-regulatory elements (CREs). While signalling pathways and GRNs are evolutionary constrained, CREs are poorly conserved at the sequence level, posing the question which cis-regulatory mechanisms facilitate coordinated and conserved gene expression patterns during animal development and evolution. CREs and their target genes are spatially restricted into conserved 3D chromatin structures suggesting a possible link between the less conserved CREs and highly conserved gene expression patterns.
In this proposal, I aim to identify CREs that differentially respond to signalling cascades. Novel approaches, such as HiChIP and capture Hi-C, will be applied to decipher the chromatin structure of the associated CREs and their target genes. The application of this approach in two distantly related vertebrate model organisms will allow me to gain insight into genome-wide evolutionary conserved nodes of GRNs controlled by these pathways. Furthermore, detailed analysis of chromatin structures induced by activation or inhibition of signaling cascades will further contribute to understanding of co-dependency and complementarity of genome architecture, cis-regulatory information, and signalling pathways. 3Dcis research will shed light on the mechanisms driving conserved gene expression patterns and common body structures, but also the constraints that different animal lineages have faced during their evolutionary path. Finally, the results will make ground breaking advances in our understanding of how cis-regulatory information and structure of our genome translate into function



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