Final Report Summary - CHROMOCOND (A molecular view of chromosome condensation)
Eukaryotic cells inherit much of their genomic information in the form of chromosomes during cell division. Centimetre-long DNA molecules are packed into micrometer-sized chromosomes to enable this process. How DNA is organised within mitotic chromosomes was still largely unknown.
A key structural protein component of mitotic chromosomes, implicated in their compaction, is the ‘condensin’ complex. In this research programme, we have worked towards elucidating the molecular architecture of mitotic chromosomes, taking advantage of new genomic techniques and the relatively simple genome organisation of yeast model systems.
We have placed particular emphasis on elucidating the contribution of the condensin complex, and the cell cycle regulation of its activities, in promoting chromosome condensation. While our previous work had provided genome-wide maps of condensin binding to budding and fission yeast chromosomes, we have now discovered the molecular determinant for condensin binding sites in the form of the RSC chromatin remodelling complex. We have analysed how condensin mediates DNA compaction by generating chromosome-wide DNA/DNA proximity maps using the 4C technique. High throughput sequencing of interaction points has provided a first glimpse of condensin binding sites as condensin-dependent interaction hubs within chromosomes.
We have complemented our experimental approach by mathematical modelling of the condensation process. This has led us to a quasi-molecular picture of what the inside of a chromosome is likely to look like.
In addition to chromosome condensation, condensin is required for resolution of sister chromatids in anaphase. We have developed an assay to study the catenation status of sister chromatids and were for the first time able to directly show how condensin contributes to their topological resolution. We have also begun to describe the contribution of condensin’s ATP-dependent activities, and cell cycle-dependent post-translational modifications to the chromosome condensation process.
A key structural protein component of mitotic chromosomes, implicated in their compaction, is the ‘condensin’ complex. In this research programme, we have worked towards elucidating the molecular architecture of mitotic chromosomes, taking advantage of new genomic techniques and the relatively simple genome organisation of yeast model systems.
We have placed particular emphasis on elucidating the contribution of the condensin complex, and the cell cycle regulation of its activities, in promoting chromosome condensation. While our previous work had provided genome-wide maps of condensin binding to budding and fission yeast chromosomes, we have now discovered the molecular determinant for condensin binding sites in the form of the RSC chromatin remodelling complex. We have analysed how condensin mediates DNA compaction by generating chromosome-wide DNA/DNA proximity maps using the 4C technique. High throughput sequencing of interaction points has provided a first glimpse of condensin binding sites as condensin-dependent interaction hubs within chromosomes.
We have complemented our experimental approach by mathematical modelling of the condensation process. This has led us to a quasi-molecular picture of what the inside of a chromosome is likely to look like.
In addition to chromosome condensation, condensin is required for resolution of sister chromatids in anaphase. We have developed an assay to study the catenation status of sister chromatids and were for the first time able to directly show how condensin contributes to their topological resolution. We have also begun to describe the contribution of condensin’s ATP-dependent activities, and cell cycle-dependent post-translational modifications to the chromosome condensation process.