Cis-regulatory landscape dynamics in development and disease

Our research focuses on mechanisms of how genes are switched on and off at a particular tissue and at a precise time point. This spatio-temporal control of gene expression is crucial during embryonic development and a prerequisite for the generation of different cell types that built the animal body plan. Key regulators in this process are cis-regulatory elements, such as enhancers that act as switches in the genome to regulate gene expression and that constitute the regulatory landscapes of developmental genes. This regulatory information is organized by the three-dimensional (3D) chromatin structure in animal genomes that ensures the correct enhancer regulates its target gene.

We aim at understanding the functional relationship between enhancers, gene expression, and 3D chromatin structure in an in vivo context, in particular zebrafish. Specifically, we apply CRISPR-Cas genome editing to dissect the role of 3D chromatin structure mediated by key architectural proteins, such as the DNA-binding factor CTCF, at a tissue-resolution level and within a whole organism (Figure 1). To do so, we combine epigenomic and transcriptomic approaches with single-cell experiments and chromosome-conformation-capture technologies to elucidate how 3D chromatin structure “feeds” distinct cell stimuli into developmental and cell differentiation programs.