Chromosome Biology: Different Turfs for Cohesin and Condensin

RESEARCH HIGHLIGHTS

Nature Reviews Molecular Cell Biology | Published online 23 Aug 2017; doi:10.1038/nrm.2017.90

PhotoDisc/ Getty Images CHROMOSOME BIOLOGY Different turfs for cohesin and condensin The structural maintenance of chromosomes (SMC) Owing to the low level of chromosome compaction complexes cohesin and condensin are ring-shaped in budding yeast, the only region with readily protein machines that encircle the chromatin and visible compaction is the megabase array of mitotic control various aspects of chromosome function, ribosomal DNA (rDNA) repeats in chromosome XII, chromosome including the formation of chromatin loops, sister which is known to accumulate excessive levels of chromatid cohesion and mitotic chromosome sister chromatid intertwines and thus requires compaction compaction. Schalbetter et al. now show that in the additional compaction to facilitate its segregation. results budding yeast Saccharomyces cerevisiae, mitotic Mitotic compaction of the region between from the chromosome compaction is achieved through centromere XII and the rDNA repeats was formation in cis-chromatin looping, and that cohesin and dependent on condensin, but the mode of condensin have distinct roles in this process. compaction was distinct from that mediated by cis of <100 kb The authors employed Hi-C (genome-wide cohesin: condensin enabled the formation of chromatin chromosome conformation capture) to study chromatin contacts >100 kb apart but had no role loops mitotic chromosome compaction. Hi-C contact in the formation of contacts that are <100 kb apart. maps produced from synchronized populations of Centromeres also require condensin function, as its yeast cells arrested in G1 or mitosis revealed that deactivation led to more contacts between the frequency of contacts along chromosome arms centromeres of different chromosomes and between regions <100 kb apart was markedly decreased the resolution between centromeric increased during mitosis, whereas the frequency of regions of different chromosomes. longer-range intra-chromosomal contacts was Together, the data indicate that in budding reduced. This suggested that mitotic chromosome yeast mitotic chromosome compaction is achieved compaction results from the formation in cis of through cis-looping and that cohesin and <100 kb chromatin loops. Chromatin compaction condensin perform distinct roles in this process: required only a third of the genome to be cohesin is responsible for achieving relatively low organized into loops, in contrast to metazoan levels of chromatin compaction genome-wide by chromosomes, in which the entire genome is forming small chromatin loops, whereas condensin organized into loops. This could explain the supports higher chromatin compaction at specific lower levels of mitotic chromosome compaction loci by forming larger chromatin loops. Condensin seen in budding yeast compared with function in yeast is similar to that of condensin in metazoan chromosomes. the longer and more repetitive metazoan Next, the function of cohesin and condensin in chromosomes, which require higher levels forming cis-loops was examined by expressing of compaction. inactive mutant complexes in mitotically arrested In another study, Kakui et al. show that in the cells. Disruption of cohesin function prevented fission yeast Schizosaccharomyces pombe, chromatin condensation and led to Hi-C maps that condensin mediates mitotic chromosome resembled those of cells arrested in G1. Thus, condensation by forming long-range chromatin cohesin promotes the formation of chromatin interactions. These long-range interactions replace loops along chromosome arms that are required the local chromatin contacts of interphase for mitotic chromatin condensation. This function chromosomes, thereby leading to reduced of cohesin is independent of its role in mediating chromatin motility during mitosis. sister chromatid cohesion, as chromatin Eytan Zlotorynski compaction was still observed in mitotic cells in ORIGINAL ARTICLES Schalbetter, S. A. et al. Structural maintenance of which DNA replication and the formation of sister chromosome complexes differentially compact mitotic chromosomes chromatids were blocked. according to genomic context. Nat. Cell Biol. http://dx.doi.org/10.1038/ Condensin deactivation did not cause ncb3594 (2017) | Kakui, Y., Rabinowitz, A., Barry, D.J. & Uhlmann, F. Condensin-mediated remodeling of the mitotic chromatin landscape genome-wide loss of mitotic compaction. Instead, in fission yeast. Nat. Genet. http://dx.doi.org/10.1038/ng.3938 (2017) condensin was necessary for higher-order FURTHER READING Uhlmann, F. SMC complexes: from DNA to chromatin compaction in specific genomic regions. chromosomes. Nat. Rev. Mol. Cell Biol. 17, 399–412 (2016)