Cohesin dependent compaction of mitotic chromosomes

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 budding yeast. The canonical role of cohesins is to co-align sister chromatids whilst condensins generally compact mitotic chromosomes. We find strikingly different roles in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosomes arms, independent of and in addition to its role in sister-chromatid cohesion. Cohesin dependent mitotic chromosome compaction can be fully accounted for through cis-looping of chromatin by loop extrusion. Second, condensin is dispensable for compaction along chromosomal arms and instead plays a specialized role, structuring rDNA and peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that SMC-dependent looping is readily deployed in a range of contexts to functionally organize chromosomes. Highlights Cohesin compacts mitotic chromosomes independently of sister chromatid cohesion. Formation of cis-loops by loop extrusion fully accounts for cohesin-mediated compaction. Condensin is not required for mitotic chromosome compaction of yeast chromosome arms Condensin has a focused pre-anaphase role at centromeres and rDNA in yeast

[1]  Tomoko Nishiyama,et al.  Cohesin acetylation and Wapl‐Pds5 oppositely regulate translocation of cohesin along DNA , 2016, The EMBO journal.

[2]  Maxim I Molodtsov,et al.  Rapid movement and transcriptional re‐localization of human cohesin on DNA , 2016, The EMBO journal.

[3]  L. Mirny,et al.  Formation of Chromosomal Domains in Interphase by Loop Extrusion , 2015, bioRxiv.

[4]  D. Koshland,et al.  Single-Molecule Imaging Reveals a Collapsed Conformational State for DNA-Bound Cohesin. , 2016, Cell reports.

[5]  L. Mirny,et al.  Chromosome Compaction by Active Loop Extrusion , 2016, Biophysical journal.

[6]  F. Uhlmann.  SMC complexes: from DNA to chromosomes , 2016, Nature Reviews Molecular Cell Biology.

[7]  E. Watrin,et al.  Gene regulation and chromatin organization: relevance of cohesin mutations to human disease. , 2016, Current opinion in genetics & development.

[8]  L. Mirny,et al.  The 3D Genome as Moderator of Chromosomal Communication , 2016, Cell.

[9]  T. Hirano,et al.  Condensin-Based Chromosome Organization from Bacteria to Vertebrates , 2016, Cell.

[10]  K. Nasmyth,et al.  Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening , 2016, Molecular cell.

[11]  K. Nasmyth,et al.  Releasing Activity Disengages Cohesin’s Smc3/Scc1 Interface in a Process Blocked by Acetylation , 2016, Molecular cell.

[12]  Anton Goloborodko,et al.  Compaction and segregation of sister chromatids via active loop extrusion , 2016, bioRxiv.

[13]  F. Uhlmann,et al.  DNA Entry into and Exit out of the Cohesin Ring by an Interlocking Gate Mechanism , 2015, Cell.

[14]  V. Guacci,et al.  The ATPases of cohesin interface with regulators to modulate cohesin-mediated DNA tethering , 2015, eLife.

[15]  Neva C. Durand,et al.  Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes , 2015, Proceedings of the National Academy of Sciences.

[16]  J. Dekker,et al.  Hi-C in Budding Yeast. , 2015, Cold Spring Harbor protocols.

[17]  Kim Nasmyth,et al.  Biological chromodynamics: a general method for measuring protein occupancy across the genome by calibrating ChIP-seq , 2015, Nucleic acids research.

[18]  M. Prentiss,et al.  Chromosomes Progress to Metaphase in Multiple Discrete Steps via Global Compaction/Expansion Cycles , 2015, Cell.

[19]  R. Skibbens,et al.  Pds5 regulators segregate cohesion and condensation pathways in Saccharomyces cerevisiae , 2015, Proceedings of the National Academy of Sciences.

[20]  K. Nasmyth,et al.  Condensin confers the longitudinal rigidity of chromosomes , 2015, Nature Cell Biology.

[21]  B. Oh,et al.  SMC condensin entraps chromosomal DNA by an ATP hydrolysis dependent loading mechanism in Bacillus subtilis , 2015, eLife.

[22]  Carmay Lim,et al.  A simple biophysical model emulates budding yeast chromosome condensation , 2015, eLife.

[23]  V. Guacci,et al.  A Conserved Domain in the Scc3 Subunit of Cohesin Mediates the Interaction with Both Mcd1 and the Cohesin Loader Complex , 2015, PLoS genetics.

[24]  Fang Wang,et al.  A high-sensitivity phospho-switch triggered by Cdk1 governs chromosome morphogenesis during cell division , 2015, Genes & development.

[25]  S. Gruber.  Multilayer chromosome organization through DNA bending, bridging and extrusion. , 2014, Current opinion in microbiology.

[26]  Jill M Dowen,et al.  Control of Cell Identity Genes Occurs in Insulated Neighborhoods in Mammalian Chromosomes , 2014, Cell.

[27]  Job Dekker,et al.  Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe , 2014, Nature.

[28]  Job Dekker,et al.  Organization of the Mitotic Chromosome , 2013, Science.

[29]  J. Ellenberg,et al.  Wapl is an essential regulator of chromatin structure and chromosome segregation , 2013, Nature.

[30]  Diwakar Shukla,et al.  OpenMM 4: A Reusable, Extensible, Hardware Independent Library for High Performance Molecular Simulation. , 2013, Journal of chemical theory and computation.

[31]  Christophe Zimmer,et al.  A Predictive Computational Model of the Dynamic 3D Interphase Yeast Nucleus , 2012, Current Biology.

[32]  John F. Marko,et al.  Self-organization of domain structures by DNA-loop-extruding enzymes , 2012, Nucleic acids research.

[33]  L. Mirny,et al.  Iterative Correction of Hi-C Data Reveals Hallmarks of Chromosome Organization , 2012, Nature Methods.

[34]  K. Nasmyth,et al.  Cohesin’s DNA Exit Gate Is Distinct from Its Entrance Gate and Is Regulated by Acetylation , 2012, Cell.

[35]  T. Hirano.  Condensins: universal organizers of chromosomes with diverse functions. , 2012, Genes & development.

[36]  F. Alber,et al.  Physical tethering and volume exclusion determine higher-order genome organization in budding yeast , 2012, Genome research.

[37]  K. Nasmyth,et al.  Cohesin's Concatenation of Sister DNAs Maintains Their Intertwining , 2011, Molecular cell.

[38]  C. Haering,et al.  Condensin structures chromosomal DNA through topological links , 2011, Nature Structural &Molecular Biology.

[39]  Kerry Bloom,et al.  Cohesin, condensin, and the intramolecular centromere loop together generate the mitotic chromatin spring , 2011, The Journal of cell biology.

[40]  Toni Gabaldón,et al.  A Midzone-Based Ruler Adjusts Chromosome Compaction to Anaphase Spindle Length , 2011, Science.

[41]  Christophe Zimmer,et al.  Principles of chromosomal organization: lessons from yeast , 2011, The Journal of cell biology.

[42]  J. J. Ward,et al.  Condensins Promote Chromosome Recoiling during Early Anaphase to Complete Sister Chromatid Separation , 2010, Developmental cell.

[43]  David A. Orlando,et al.  Mediator and Cohesin Connect Gene Expression and Chromatin Architecture , 2010, Nature.

[44]  William Stafford Noble,et al.  A Three-Dimensional Model of the Yeast Genome , 2010, Nature.

[45]  P. Fraser,et al.  Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus , 2009, Nature.

[46]  W. Earnshaw,et al.  Condensin: Architect of mitotic chromosomes , 2009, Chromosome Research.

[47]  J. Gerton,et al.  Intersection of ChIP and FLIP, genomic methods to study the dynamics of the cohesin proteins , 2009, Chromosome Research.

[48]  Job Dekker,et al.  Mapping in Vivo Chromatin Interactions in Yeast Suggests an Extended Chromatin Fiber with Regional Variation in Compaction* , 2008, Journal of Biological Chemistry.

[49]  D. Engelke,et al.  Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes. , 2008, Genes & development.

[50]  K. Shirahige,et al.  Condensin-Dependent rDNA Decatenation Introduces a Temporal Pattern to Chromosome Segregation , 2008, Current Biology.

[51]  K. Nasmyth,et al.  The cohesin ring concatenates sister DNA molecules , 2008, Nature.

[52]  P. Megee,et al.  The enhancement of pericentromeric cohesin association by conserved kinetochore components promotes high-fidelity chromosome segregation and is sensitive to microtubule-based tension. , 2007, Genes & development.

[53]  Kim Nasmyth,et al.  Structure and stability of cohesin's Smc1-kleisin interaction. , 2004, Molecular cell.

[54]  F. Uhlmann,et al.  Cdc14 Phosphatase Induces rDNA Condensation and Resolves Cohesin-Independent Cohesion during Budding Yeast Anaphase , 2004, Cell.

[55]  R. Gassmann,et al.  Condensin is required for nonhistone protein assembly and structural integrity of vertebrate mitotic chromosomes. , 2003, Developmental cell.

[56]  D. Koshland,et al.  In vivo dissection of the chromosome condensation machinery , 2002, The Journal of cell biology.

[57]  A. Murray,et al.  Mutation of YCS4, a budding yeast condensin subunit, affects mitotic and nonmitotic chromosome behavior. , 2002, Molecular biology of the cell.

[58]  C. Sunkel,et al.  A role for Drosophila SMC4 in the resolution of sister chromatids in mitosis , 2001, Current Biology.

[59]  V. Guacci,et al.  Pds5p Is an Essential Chromosomal Protein Required for Both Sister Chromatid Cohesion and Condensation in Saccharomyces cerevisiae , 2000, The Journal of cell biology.

[60]  A. Strunnikov,et al.  The Condensin Complex Governs Chromosome Condensation and Mitotic Transmission of Rdna , 2000, The Journal of cell biology.

[61]  J. Diffley,et al.  DNA synthesis at individual replication forks requires the essential initiation factor Cdc45p , 2000, The EMBO journal.

[62]  O. A. Cabello,et al.  Chromosome condensation factor Brn1p is required for chromatid separation in mitosis. , 2000, Molecular biology of the cell.

[63]  G. Goshima,et al.  Establishing Biorientation Occurs with Precocious Separation of the Sister Kinetochores, but Not the Arms, in the Early Spindle of Budding Yeast , 2000, Cell.

[64]  Friedrich Lottspeich,et al.  Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1 , 1999, Nature.

[65]  V. Guacci,et al.  A Direct Link between Sister Chromatid Cohesion and Chromosome Condensation Revealed through the Analysis of MCD1 in S. cerevisiae , 1997, Cell.

[66]  K. Nasmyth,et al.  Cohesins: Chromosomal Proteins that Prevent Premature Separation of Sister Chromatids , 1997, Cell.

[67]  V. Guacci,et al.  Chromosome condensation and sister chromatid pairing in budding yeast , 1994, The Journal of cell biology.

[68]  A. Riggs,et al.  DNA methylation and late replication probably aid cell memory, and type I DNA reeling could aid chromosome folding and enhancer function. , 1990, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[69]  U. K. Laemmli,et al.  Architecture of metaphase chromosomes and chromosome scaffolds , 1983, The Journal of cell biology.

[70]  J. R. Paulson,et al.  The structure of histone-depleted metaphase chromosomes , 1977, Cell.

[71]  Vijay S. Pande,et al.  Efficient nonbonded interactions for molecular dynamics on a graphics processing unit , 2010, J. Comput. Chem..

[72]  D. Koshland,et al.  In vivo requirements for rDNA chromosome condensation reveal two cell-cycle-regulated pathways for mitotic chromosome folding. , 2004, Genes & development.

[73]  K. Nasmyth.  THE GENOME : Joining , Resolving , and Separating Sister Chromatids During Mitosis and Meiosis , 2006 .