%0 Thesis
%A Domínguez Acemel, Rafael
%T The role of the 3D architecture of the nucleus in shaping vertebrate transcriptional regulation
%D 2019
%U http://hdl.handle.net/10433/7087
%X Animal morphological diversity is astonishing and it is partially due to differences in gene expres-sion between different species during development. Recently, the genome folding in TopologicallyAssociated Domains (TADs) found in most animals has been shown to be critical in the controlof transcription during development. Distal enhancers are able to interact with the promoters ofdevelopmental genes only when they belong to the same 3D environment or TAD. Therefore, weinvestigated how changes in the 3D folding of the genome could have impacted the changes in generegulation responsible for the evolution of vertebrates. In order to do so we combined syntenicanalysis with Chromatin Conformation Capture experiments such as 4C-seq and HiChIP.First we compared the chromatin folding around the zebrafish HoxD and the amphioxus Hoxloci using 4C-seq experiments coupled to computational modelling. The chromatin architecturearound the vertebrate HoxD locus is peculiar, with al the HoxD genes located at the boundarybetween two TADs allowing them to switch to respond to distal enhancers located in either ofthe two TADs during the patterning of the limbs. In contrast, all the amphioxus Hox genesbelong to the same TAD. However, the region located downstream from Hox1 is homologous tothe vertebrate anterior TAD and is wired both in 3D and functionally to the regulation of Hoxgenes also in amphioxus. This suggests a stepwise evolution of the chromatin folding in two TADsfound in extant vertebrates, with the anterior TAD being already wired to Hox genes in the lastcommon ancestor of chordates.Second we performed a genome wide comparison of the chromatin folding between zebrafish andamphioxus using HiChIP and antibodies against different histone modifications. Using H3K4me3HiChIP experiments we were able to identify the Regulatory Landscapes (RLs) of all active devel-opmental promoters using a single experiment. By doing so we were able to identify almost fourhundred cases of chromosomal rearrangements that potentially altered the boundaries of a TADand were susceptible to generate regulatory novelties in the vertebrate lineage. Also, we found thatthe two events of whole genome duplication that occurred at the root of vertebrates allowed someof the paralog genes originated to increase their RLs both in size and in number of enhancers.
%K Diversidad morfológica
%K Genética del desarrollo
%K Vertebrados
%~