Schalbetter Stephanie Andrea, Goloborodko Anton, Fudenberg Geoffrey, Belton Jon-Matthew, Miles Catrina, Yu Miao, Dekker Job, Mirny Leonid, Baxter Jonathan
Genome Damage and Stability Centre, Science Park Road, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
Institute for Medical Engineering and Sciences, Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nat Cell Biol. 2017 Sep;19(9):1071-1080. doi: 10.1038/ncb3594. Epub 2017 Aug 21.
Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead, it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes.
染色体结构维持（SMC）蛋白复合物是染色体构象的关键决定因素。利用Hi-C和聚合物建模，我们研究了黏连蛋白和凝聚蛋白这两种高度保守的SMC复合物如何在芽殖酵母酿酒酵母中组织染色体。黏连蛋白的典型作用是使姐妹染色单体共对齐，而凝聚蛋白通常使有丝分裂染色体浓缩。我们发现这两种复合物在芽殖酵母有丝分裂中具有截然不同的作用。首先，黏连蛋白负责压缩有丝分裂染色体臂，而不依赖于姐妹染色单体黏连。聚合物模拟表明，这种作用可以通过染色质的顺式环化完全解释。其次，凝聚蛋白对于沿着染色体臂的压缩通常是可有可无的。相反，它在压缩核糖体DNA近端区域和促进着丝粒周围区域的分离方面发挥着靶向作用。我们的结果表明，SMC复合物的保守机制是形成染色质环，并且不同的依赖于SMC的环化活动被选择性地用于适当地压缩染色体。
