¹Stowers Institute for Medical Research, 1000 E. 50th St. Kansas City, MO 64110

²Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Box B121, 4200 E. Ninth Ave., Denver, CO 80262

³Department of Biochemistry and Biophysics, University of California, 600 16th St, San Francisco, CA 94107-2240

⁴Howard Hughes Medical Institute, Department of Embryology, Carnegie Institution of Washington, 115 W. University Parkway, Baltimore, MD 21210.

Methodology/Principle Findings: We have used chromatin immunoprecipitation coupled with microarray analysis (ChIP chip) to produce a genome-wide description of cohesin binding to meiotic and mitotic chromosomes of S. cerevisiae. A computer program, PeakFinder, enables flexible, automated identification and annotation of cohesin binding peaks in ChIP chip data.

Conclusions/Significance: Cohesin sites are highly conserved in meiosis and mitosis, suggesting that chromosomes share a common underlying structure during different developmental programs. These sites occur with a semi-periodic spacing of 11 kb that correlates with AT content. The number of sites correlates with chromosome size; however, binding to neighboring sites does not appear to be cooperative. We observed a very strong correlation between cohesin sites and regions between convergent transcription units. The apparent incompatibility between transcription and cohesin binding exists in both meiosis and mitosis. Further experiments reveal that transcript elongation into a cohesin binding site removes cohesin. A negative correlation between cohesin sites and meiotic recombination sites suggests meiotic exchange is sensitive to the chromosome structure provided by cohesin. The genome-wide view of mitotic and meiotic cohesin binding provides an important framework for the exploration of cohesins and cohesion in other genomes.