This PhD project aims to better understand the three-dimensional organization of animal genomes, and more specifically the dynamics and formation of nuclear compartments.
DNA, which carries genetic information, is folded within the cell nucleus. The genome is organized into two main nuclear compartments that are linked to gene expression and therefore potentially involved in the establishment of phenotypes. However, the causal relationship between nuclear compartments and gene expression remains unclear, and the molecular mechanisms that form and maintain nuclear compartments have not yet been elucidated.
In the first aim, we hypothesize that differences in nuclear compartmentalization between individuals during development play a role in the establishment of phenotypes. The variability of genome organization in wild-type bovine embryonic stem cells and those carrying mutations associated with a specific phenotype, the polled phenotype, will be studied during stem cell differentiation (Hi-C, ChIP-seq, ATAC-seq, RNA-seq).
The second aim will study the molecular mechanisms underlying the formation of nuclear compartments. To this end, a nuclear compartment will be artificially created by recruiting a histone mark to a specific genomic region. The maintenance of the nuclear compartment will be studied throughout cell cycles and differentiation.
Overall, this research will deepen our understanding of the molecular mechanisms underlying the formation and maintenance of nuclear compartments, as well as provide greater insight into the role of nuclear compartmentalization in the establishment of phenotypes.
