CSC/IC Microarray Centre Seminar Series

Dr Frank Uhlmann
Chromosome Segregation Laboratory, Cancer Research Institute London

Title: Use of high density oligonucleotide arrays to study chromosome architecture in yeast

All eukaryotes contain three essential structural maintenance of chromosomes (SMC)-subunit containing chromosomal protein complexes. We have analysed two of these complexes, called ‘cohesin’ and ‘condensin’. These are instrumental in many crucial chromosomal functions, including sister chromatid cohesion, chromosome condensation, chromatin boundary formation, transcriptional regulation and DNA repair. The SMC complexes show a striking ring-shaped architecture and may bind to DNA by topological embrace. How DNA binding by these complexes mediates their biological function is still poorly understood. To gain insight into the way by which cohesin and condensin work on chromosomes, we have asked exactly where along chromosomes these complexes bind. This was facilitated by technological advances over the last years that have made genome-wide high resolution oligonucleotide tiling arrays available for both budding and fission yeast. We have therefore used chromatin immunoprecipitation from these species followed by hybridisation to such microarrays to analyse the binding patterns of the two SMC complexes. We found that both cohesin and condensin are initially recruited to chromosomes by an SMC loading factor, consisting of the Scc2 and Scc4 proteins. These loading sites correlate with highly transcribed genes, in particular tRNA genes. From the sites of loading, cohesin moves away towards sites of convergent transcriptional termination, in a fashion consistent with sliding of the cohesin ring along the chromosome. In contrast condensin remains associated with the loading sites in a dynamic fashion. I will discuss the implications of these patterns for the architecture of eukaryotic chromosomes.

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