Evolutionary insights into primate gene regulation and development of methods to study DNA modifications

Changes in the epigenetic regulation of gene expression have important implications for evolution. However, the study of these changes (i) has not been consistently assessed across closely related species, (ii) oftentimes has ignored evolutionarily relevant genomic regions, and (iii) has been limite...

Full description

Bibliographic Details
Author: Esteller Cucala, Paula
Format: doctoral thesis
Status:Published version
Publication Date:2023
Country:España
Institution:CBUC, CESCA
Repository:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/688164
Online Access:http://hdl.handle.net/10803/688164
Access Level:Open access
Keyword:Gene regulation
Primates
Methylation
Long-read sequencing
EOH-seq
Regulació de gens
Primats
Metilació
Seqüenciació de lectura llarga
575
Description
Summary:Changes in the epigenetic regulation of gene expression have important implications for evolution. However, the study of these changes (i) has not been consistently assessed across closely related species, (ii) oftentimes has ignored evolutionarily relevant genomic regions, and (iii) has been limited to specific epigenetic features. In this thesis, we have explored gene regulation through the lens of primate evolution and human populations. Namely, we characterized a panel of lymphoblastoid cell lines (LCL) from five primates and highlighted the particularly relevant role of weak regulatory elements in evolution. We then studied DNA methylation, a particular epigenetic mechanism, in a structurally complex chromosome –the Y chromosome– across 7 major human haplogroups. Finally, we developed an experimental methodology to detect and discriminate different DNA modifications. Specifically, we present EOH-seq and sEM-seq, two complementary methods for the whole-genome study of 5hmC and 5mC that can be applied to a variety of different conditions, cell types, and species.