Video showing a structural model of the X chromosome from one particular white blood cell (courtesy of Dr. Tim Stevens, Laboratory of Molecular Biology, Cambridge). Regions of the chromosome are coloured blue where genes are active and yellow where it associates with a protein called Lamin-B1 in the membrane that surrounds the nucleus.
In order to gain a more system-wide view of chromatin structure within the cell we are exploiting similar computational approaches (to those used to determine structural models of protein complexes) to studies of the global structure of the genome. In chromatin conformation capture (3C) experiments, such as Hi-C, restriction fragment digestion of DNA in intact nuclei is followed by the ligation of free DNA ends that are in close 3D spatial proximity. These ligated DNA junctions are then identified by high-throughput sequencing to provide distance restraints for structure calculations of chromatin architecture in the nucleus. Our initial studies of the 3D structure of the X chromosome in stably differentiated cells have illustrated the spatial partitioning of the chromosome into inactive regions that associate with the nuclear membrane and regions that contain active genes (see Video).
For further details see: Nagano et al., Nature, 2013, 502: 59-64.
Members of our group currently involved in this project are: Liam Atkinson, Kai Wohlfahrt, in collaboration with Dr Tim Stevens (Laboratory of Molecular Biology, Cambridge)