RRC ID 65190
Author Woglar A, Yamaya K, Roelens B, Boettiger A, Köhler S, Villeneuve AM.
Title Quantitative cytogenetics reveals molecular stoichiometry and longitudinal organization of meiotic chromosome axes and loops.
Journal PLoS Biol
Abstract During meiosis, chromosomes adopt a specialized organization involving assembly of a cohesin-based axis along their lengths, with DNA loops emanating from this axis. We applied novel, quantitative, and widely applicable cytogenetic strategies to elucidate the molecular bases of this organization using Caenorhabditis elegans. Analyses of wild-type (WT) chromosomes and de novo circular minichromosomes revealed that meiosis-specific HORMA-domain proteins assemble into cohorts in defined numbers and co-organize the axis together with 2 functionally distinct cohesin complexes (REC-8 and COH-3/4) in defined stoichiometry. We further found that REC-8 cohesins, which load during S phase and mediate sister-chromatid cohesion, usually occur as individual complexes, supporting a model wherein sister cohesion is mediated locally by a single cohesin ring. REC-8 complexes are interspersed in an alternating pattern with cohorts of axis-organizing COH-3/4 complexes (averaging 3 per cohort), which are insufficient to confer cohesion but can bind to individual chromatids, suggesting a mechanism to enable formation of asymmetric sister-chromatid loops. Indeed, immunofluorescence/fluorescence in situ hybridization (immuno-FISH) assays demonstrate frequent asymmetry in genomic content between the loops formed on sister chromatids. We discuss how features of chromosome axis/loop architecture inferred from our data can help to explain enigmatic, yet essential, aspects of the meiotic program.
Volume 18(8)
Pages e3000817
Published 2020-8-1
DOI 10.1371/journal.pbio.3000817
PII PBIOLOGY-D-20-01207
PMID 32813728
PMC PMC7458323
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Cycle Proteins / genetics* Cell Cycle Proteins / metabolism Chromatids / metabolism Chromatids / ultrastructure* Chromosomal Proteins, Non-Histone / genetics* Chromosomal Proteins, Non-Histone / metabolism Chromosome Segregation Chromosomes / metabolism Chromosomes / ultrastructure* Cohesins Cytogenetic Analysis In Situ Hybridization, Fluorescence Meiosis* S Phase / genetics Synaptonemal Complex / metabolism Synaptonemal Complex / ultrastructure*
Resource
C.elegans tm1814 tm1857 tm3655 tm2543