The correct temporal and spatial patterns of gene expression of Hox genes are necessary for patterning of the developing embryo. Intriguingly, the time and place of Hox gene expression is collinear with the order of the genes on the chromosome. However, t he molecular mechanisms underlying this exquisite gene regulation are poorly understood. In cell culture, the sequential activation of mouse HoxB genes correlates with a visible unfolding of chromatin structure, and a re-localisation of active genes within the nucleus. I want to understand the mechanisms that underpin these large-scale changes in chromatin and nuclear organisation, by combining fluorescence in situ hybridisation (FISH) with mouse models of Hox gene regulation. To do this I will firstly identify cis-acting genomic elements that regulate the nuclear reorganisation of HoxB. I also propose to ask whether other Hox clusters behave similarly, by analysing the nuclear behaviour of HoxD in vivo, in the embryo. These experiments should provide mechanistic insight into colinear gene expression.
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