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Title: Nuclear organisation in stem cells
Author: Wiblin, Annie E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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If nuclear organisation regulates gene expression, then it may have a role in gene silencing as a cell commits to differentiation. It is therefore important to determine the nuclear organisation of stem cells. Here I ask if the nuclear architecture of human and mouse embryonic stem (ES) cells is different from that of differentiated cells? I have examined the position of chromosomes 18 (gene-poor) and 19 (gene-rich) and show that their radial nuclear organisation, seen in differentiated cells, is already established in human ES cells. However, I show that the position of centromeres is different in ES cells and differentiated cells. I have investigated the location of two gene dense regions, 11p15 and 6p21 (which contains the pluripotent gene OCT4) and the 12p13 region (containing NANOG), in differentiated and human ES cells. I show that although the position of gene dense regions is maintained through differentiation, specific genes involved in pluripotency change position either within the nucleus or relative to their chromosome territories. In parallel I have established data on nuclear reorganisation during differentiation of murine ES cells towards an ectodermal lineage. I show the relocalisation of chromosome territories and genes involved in neuronal development during differentiation, which is accompanied by substantial clustering of centromeric heterochromatin. Using mutant mouse ES cells I show that clustering still occurs in cells the lack DNA methylation, the DNA binding protein MeCP2 and the Suv39h histone methyltransferase. I conclude that although some of the basic principles of nuclear organisation are already established in ES cells, spatial reorganisation of the genome is evident during differentiation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available