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Title: The evolution of chromatin folding in mammals : a role for CTCF
Author: Vietri Rudan, M.
ISNI:       0000 0004 8502 5986
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2015
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The organisation of the DNA inside eukaryotic cell nuclei is not random. Rather than being intermingled with one another, chromosomes are compacted in a hierarchical manner which is conserved throughout eukaryote evolution. Topological domains have recently emerged as key architectural building blocks of chromosomes in complex genomes. This thesis aimed to explore the evolutionary dynamics of chromatin architecture in order to shed light on its functional relevance and on how architectural proteins can shape it. Comparative Hi-C in liver cells from four mammalian species was used to characterise conservation and divergence of chromosomal structure within distantly related genomes. Results show that the modular organisation of chromosomes is robustly conserved in syntenic regions, and that domain structure is maintained during chromosomal rearrangements. This conservation is compatible with the evolution of the binding landscape of the architectural protein CTCF. Specifically, conserved CTCF sites are more often co-localised with cohesin, enriched at strong topological domain borders and bind to DNA motifs that are under strong selection. Interestingly, CTCF binding sites which are divergent between species are strongly correlated with divergence of internal domain structure. This divergence is likely driven by CTCF binding sequence changes, demonstrating how genome evolution can be linked directly with a continuous flux of local chromosome conformation changes. Finally, the architectural activity of CTCF is cohesin- dependent and the manner in which individual CTCF/cohesin sites choose interacting partners is dictated by the orientation of the CTCF binding motif.
Supervisor: Hadjur, S. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available