Periodic Reporting for period 1 - 3Dcis (3D Organization of Functionally Conserved Cis-Regulatory Elements)
Período documentado: 2018-04-01 hasta 2020-03-31
This project aims to understand the functional relationship between enhancers, conserved gene expression patterns and 3D chromatin structure during vertebrate development and evolution. As sequence conservation of enhancers is extremely limited, we applied innovative approaches to identify and systematically compare the functional response of enhancers and gene expression across different animal lineages. We identified functionally conserved enhancers and their target genes in the distantly related vertebrate model organisms, zebrafish (Danio rerio) and the western clawed frog (Xenopus tropicalis). Assessing the underlying 3D chromatin architecture, we deciphered the chromatin structures at orthologous genomic regions and enriched our understanding of how the cis-regulatory information of enhancers and genome structure translate into function. Although enhancers are not constrained by sequence conservation, they are constrained by conserved structural properties in the nucleus. Our data pave the way towards a deeper understanding of cis-regulatory mechanisms during development and evolution but also towards a better evaluation of regulatory mutations that are frequently detected in human congenital disease and cancer.