Chromosome Structure
Chromosome Structure - Chromosomes undergo dynamic structural changes during the cell cycle and during cell differentiation that dictate the functional properties of the chromosome. One of the most dramatic examples of this is the mitotic condensation of chromosomes that is required for chromosome segregation during cell division. We currently have a very limited understanding of the higher order folding of the chromosome. The X-ray crystal structure of the nucleosome has provided a detailed understanding of the primary level of organization of the chromosome (Luger et al, Nature 1997). However, the organization of the chromosome beyond the wrapping of DNA around the nucleosome is unknown and the mechanisms that control chromosome structural rearrangement are only beginning to be deciphered.
We are developing techniques to map the higher order folding of chromosomes from the nucleosome level to the level of the condensed mitotic chromosome. These methods should allow us to interrogate the changes in chromosome structure that occur as cells divide and differentiate and as cells silence some regions of their genome while mantaining transcriptional activity in others. We are also developing methods to analyze the contribution of non-coding RNAs to the structural rearrangements in chromosomes that occur during mitosis and gene silencing. Through these approaches we hope to gain insight into the higher order organization of chromosomes and the mechanisms that control chromosome structural changes.
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