Abstract
Sister chromatids, the products of eukaryotic DNA replication, are held together by the chromosomal cohesin complex after their synthesis. This allows the spindle in mitosis to recognize pairs of replication products for segregation into opposite directions1,2,3,4,5,6. Cohesin forms large protein rings that may bind DNA strands by encircling them7, but the characterization of cohesin binding to chromosomes in vivo has remained vague. We have performed high resolution analysis of cohesin association along budding yeast chromosomes III–VI. Cohesin localizes almost exclusively between genes that are transcribed in converging directions. We find that active transcription positions cohesin at these sites, not the underlying DNA sequence. Cohesin is initially loaded onto chromosomes at separate places, marked by the Scc2/Scc4 cohesin loading complex8, from where it appears to slide to its more permanent locations. But even after sister chromatid cohesion is established, changes in transcription lead to repositioning of cohesin. Thus the sites of cohesin binding and therefore probably sister chromatid cohesion, a key architectural feature of mitotic chromosomes, display surprising flexibility. Cohesin localization to places of convergent transcription is conserved in fission yeast, suggesting that it is a common feature of eukaryotic chromosomes.
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Acknowledgements
We are indebted to E. Schwob for initiating this collaboration. We also thank A. Nakada and T. Chaplin for technical support, R. Rothstein for reagents, and J. Cau, J. Sgouros, J. Svejstrup and members of our laboratories for discussions and comments on the manuscript. A.L. was supported by an EU Marie Curie individual fellowship and a Journal of Cell Science travelling fellowship; K.S. acknowledges support through a MEXT grants-in-aid for priority areas; F.U. was supported by the EMBO Young Investigator programme.
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Supplementary information
Supplementary Figure 1
Binding of cohesin subunits to S. cerevisiae chromosome VI. (PDF 170 kb)
Supplementary Figure 2
Binding of the cohesin subunit Scc1 to S. cerevisiae chromosomes III-V at 23ºC. (PDF 821 kb)
Supplementary Figure 3
Changes in the binding of Scc1 to S. cerevisiae chromosome VI in response to transcription. (PDF 372 kb)
Supplementary Figure 4
Binding of the cohesin subunit Scc1 to S. cerevisiae chromosomes III-V after heat-shock. (PDF 769 kb)
Supplementary Figure 5
Binding of Scc2, Scc4 and transcriptional activity along S. cerevisiae chromosome VI. (PDF 150 kb)
Supplementary Figure 6
Loading of cohesin at Scc2 binding sites on S. cerevisiae chromosome VI. (PDF 146 kb)
Supplementary Note 1
Relationship of Scc2 binding and transcriptional activity along S. cerevisiae chromosome VI. (PDF 98 kb)
Supplementary Note 2
Cohesin association sites on S.pombe chromosomes 2-3. (PDF 384 kb)
Supplementary Note 3
Gene orientation analysis on S. cerevisiae chromosomes III-VI. (PDF 60 kb)
Supplementary Table 1
Cohesin association sites on S. cerevisiae chromosomes III-VI. (PDF 37 kb)
Supplementary Table 2
Strain list. (PDF 52 kb)
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Lengronne, A., Katou, Y., Mori, S. et al. Cohesin relocation from sites of chromosomal loading to places of convergent transcription. Nature 430, 573–578 (2004). https://doi.org/10.1038/nature02742
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DOI: https://doi.org/10.1038/nature02742
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