scholarly journals Cohesin Smc1β determines meiotic chromatin axis loop organization

2008 ◽  
Vol 180 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Ivana Novak ◽  
Hong Wang ◽  
Ekaterina Revenkova ◽  
Rolf Jessberger ◽  
Harry Scherthan ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Model Systems ◽  
Chromatin Loop ◽  
Loop Size ◽  
Chromatin Loops ◽  
Meiotic Chromosomes ◽  
Chromatid Cohesion ◽  
Axis Extension ◽  
Chromosome Axis ◽  
Structural Maintenance Of Chromosomes

Meiotic chromosomes consist of proteinaceous axial structures from which chromatin loops emerge. Although we know that loop density along the meiotic chromosome axis is conserved in organisms with different genome sizes, the basis for the regular spacing of chromatin loops and their organization is largely unknown. We use two mouse model systems in which the postreplicative meiotic chromosome axes in the mutant oocytes are either longer or shorter than in wild-type oocytes. We observe a strict correlation between chromosome axis extension and a general and reciprocal shortening of chromatin loop size. However, in oocytes with a shorter chromosome axis, only a subset of the chromatin loops is extended. We find that the changes in chromatin loop size observed in oocytes with shorter or longer chromosome axes depend on the structural maintenance of chromosomes 1β (Smc1β), a mammalian chromosome–associated meiosis-specific cohesin. Our results suggest that in addition to its role in sister chromatid cohesion, Smc1β determines meiotic chromatin loop organization.

scholarly journals Eco1-dependent cohesin acetylation anchors chromatin loops and cohesion to define functional meiotic chromosome domains

2021 ◽  
Author(s):  
Rachael E Barton ◽  
Lucia F Massari ◽  
Daniel Robertson ◽  
Adele L Marston
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Meiotic Chromosome ◽  
Chromatin Loops ◽  
Meiotic Chromosomes ◽  
Sister Chromatids ◽  
Gamete Formation ◽  
Chromosome Domains ◽  
Chromatid Cohesion ◽  
Cohesin Subunit

Cohesin organizes the genome by forming intra-chromosomal loops and inter-sister chromatid linkages. During gamete formation by meiosis, chromosomes are reshaped to support crossover recombination and two consecutive rounds of chromosome segregation. Here we show that Eco1 acetyltransferase positions both chromatin loops and sister chromatid cohesion to organize meiotic chromosomes into functional domains in budding yeast. Eco1 acetylates the Smc3 cohesin subunit in meiotic S phase to establish chromatin boundaries, independently of DNA replication. Boundary formation by Eco1 is critical for prophase exit and for the maintenance of cohesion until meiosis II, but is independent of the ability of Eco1 to antagonize the cohesin-release factor, Wpl1. Conversely, prevention of cohesin release by Wpl1 is essential for centromeric cohesion, kinetochore monoorientation and co-segregation of sister chromatids in meiosis I. Our findings establish Eco1 as a key determinant of chromatin boundaries and cohesion positioning, revealing how local chromosome structuring directs genome transmission into gametes.

scholarly journals Molecular organization of mammalian meiotic chromosome axis revealed by expansion STORM microscopy

2019 ◽  
Vol 116 (37) ◽  
pp. 18423-18428 ◽  
Author(s):  
Huizhong Xu ◽  
Zhisong Tong ◽  
Qing Ye ◽  
Tengqian Sun ◽  
Zhenmin Hong ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Molecular Organization ◽  
Homologous Chromosomes ◽  
Meiotic Chromosomes ◽  
C Terminus ◽  
Stochastic Optical Reconstruction Microscopy ◽  
Optical Reconstruction ◽  
20 Nm ◽  
Chromosome Axis

During prophase I of meiosis, chromosomes become organized as loop arrays around the proteinaceous chromosome axis. As homologous chromosomes physically pair and recombine, the chromosome axis is integrated into the tripartite synaptonemal complex (SC) as this structure’s lateral elements (LEs). While the components of the mammalian chromosome axis/LE—including meiosis-specific cohesin complexes, the axial element proteins SYCP3 and SYCP2, and the HORMA domain proteins HORMAD1 and HORMAD2—are known, the molecular organization of these components within the axis is poorly understood. Here, using expansion microscopy coupled with 2-color stochastic optical reconstruction microscopy (STORM) imaging (ExSTORM), we address these issues in mouse spermatocytes at a resolution of 10 to 20 nm. Our data show that SYCP3 and the SYCP2 C terminus, which are known to form filaments in vitro, form a compact core around which cohesin complexes, HORMADs, and the N terminus of SYCP2 are arrayed. Overall, our study provides a detailed structural view of the meiotic chromosome axis, a key organizational and regulatory component of meiotic chromosomes.

Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes

2000 ◽  
Vol 113 (4) ◽  
pp. 673-682 ◽  
Author(s):  
M. Eijpe ◽  
C. Heyting ◽  
B. Gross ◽  
R. Jessberger
Keyword(s):  
Gene Dosage ◽  
Dna Recombination ◽  
Immunofluorescence Analysis ◽  
Synaptonemal Complexes ◽  
Meiotic Chromosomes ◽  
Chromatid Cohesion ◽  
Specific Proteins ◽  
Experimental Approaches ◽  
Structural Maintenance Of Chromosomes ◽  
Smc Proteins

In somatic cells, the heterodimeric Structural Maintenance of Chromosomes (SMC) proteins are involved in chromosome condensation and gene dosage compensation (SMC2 and 4), and sister chromatid cohesion and DNA recombination (SMC1 and 3). We report here evidence for an involvement of mammalian SMC1 and SMC3 proteins in meiosis. Immunofluorescence analysis of testis sections showed intense chromatin association in meiotic prophase cells, weaker staining in round spermatids and absence of the SMC proteins in elongated spermatids. In spermatocyte nuclei spreads, the SMC1 and SMC3 proteins localize in a beaded structure along the axial elements of synaptonemal complexes of pachytene and diplotene chromosomes. Both SMC proteins are present in rat spermatocytes and enriched in preparations of synaptonemal complexes. Several independent experimental approaches revealed interactions of the SMC proteins with synaptonemal complex-specific proteins SCP2 and SCP3. These results suggest a model for the arrangement of SMC proteins in mammalian meiotic chromatin.

scholarly journals Crossovers trigger a remodeling of meiotic chromosome axis composition that is linked to two-step loss of sister chromatid cohesion

2008 ◽  
Vol 22 (20) ◽  
pp. 2886-2901 ◽  
Author(s):  
E. Martinez-Perez ◽  
M. Schvarzstein ◽  
C. Barroso ◽  
J. Lightfoot ◽  
A. F. Dernburg ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Meiotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Chromatid Cohesion ◽  
Chromosome Axis

scholarly journals The Multiple Roles of Cohesin in Meiotic Chromosome Morphogenesis and Pairing

2009 ◽  
Vol 20 (3) ◽  
pp. 1030-1047 ◽  
Author(s):  
Gloria A. Brar ◽  
Andreas Hochwagen ◽  
Ly-sha S. Ee ◽  
Angelika Amon
Keyword(s):  
Sister Chromatid ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Multiple Roles ◽  
Axis Formation ◽  
Chromatid Cohesion ◽  
Cohesin Subunit ◽  
Chromosome Axis ◽  
Segregation Of Chromosomes

Sister chromatid cohesion, mediated by cohesin complexes, is laid down during DNA replication and is essential for the accurate segregation of chromosomes. Previous studies indicated that, in addition to their cohesion function, cohesins are essential for completion of recombination, pairing, meiotic chromosome axis formation, and assembly of the synaptonemal complex (SC). Using mutants in the cohesin subunit Rec8, in which phosphorylated residues were mutated to alanines, we show that cohesin phosphorylation is not only important for cohesin removal, but that cohesin's meiotic prophase functions are distinct from each other. We find pairing and SC formation to be dependent on Rec8, but independent of the presence of a sister chromatid and hence sister chromatid cohesion. We identified mutations in REC8 that differentially affect Rec8's cohesion, pairing, recombination, chromosome axis and SC assembly function. These findings define Rec8 as a key determinant of meiotic chromosome morphogenesis and a central player in multiple meiotic events.

scholarly journals Quantitative Cytogenetics Reveals Molecular Stoichiometry and Longitudinal Organization of Meiotic Chromosome Axes and Loops

2019 ◽  
Author(s):  
Alexander Woglar ◽  
Kei Yamaya ◽  
Baptiste Roelens ◽  
Alistair Boettiger ◽  
Simone Köhler ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
De Novo ◽  
Meiotic Chromosome ◽  
S Phase ◽  
C Elegans ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Molecular Bases ◽  
Chromosome Axis ◽  
Specialized Organization

ABSTRACTDuring 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 C. elegans. Analyses of WT chromosomes and de novo circular mini-chromosomes revealed that meiosis-specific HORMA-domain proteins assemble into cohorts in defined numbers and co-organize the axis together with two 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 three 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, 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.

scholarly journals Transcription dynamically patterns the meiotic chromosome-axis interface

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Xiaoji Sun ◽  
Lingzhi Huang ◽  
Tovah E Markowitz ◽  
Hannah G Blitzblau ◽  
Doris Chen ◽  
...  
Keyword(s):  
Protein Binding ◽  
Budding Yeast ◽  
Meiotic Chromosome ◽  
Cohesin Complex ◽  
Protein Enrichment ◽  
Meiotic Chromosomes ◽  
Convergent Transcription ◽  
Chromosome Axis ◽  
Ubiquitous Presence ◽  
Axial Element

Meiotic chromosomes are highly compacted yet remain transcriptionally active. To understand how chromosome folding accommodates transcription, we investigated the assembly of the axial element, the proteinaceous structure that compacts meiotic chromosomes and promotes recombination and fertility. We found that the axial element proteins of budding yeast are flexibly anchored to chromatin by the ring-like cohesin complex. The ubiquitous presence of cohesin at sites of convergent transcription provides well-dispersed points for axis attachment and thus chromosome compaction. Axis protein enrichment at these sites directly correlates with the propensity for recombination initiation nearby. A separate modulating mechanism that requires the conserved axial-element component Hop1 biases axis protein binding towards small chromosomes. Importantly, axis anchoring by cohesin is adjustable and readily displaced in the direction of transcription by the transcriptional machinery. We propose that such robust but flexible tethering allows the axial element to promote recombination while easily adapting to changes in chromosome activity.

Architecture and Dynamics of Meiotic Chromosomes

2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Sarah N. Ur ◽  
Kevin D. Corbett
Keyword(s):  
Meiotic Prophase ◽  
Morphological Changes ◽  
Meiotic Chromosome ◽  
Dna Recombination ◽  
Chromosome Complement ◽  
Annual Review ◽  
Publication Date ◽  
Meiotic Chromosomes ◽  
Crystal Model ◽  
Chromosome Axis

The specialized two-stage meiotic cell division program halves a cell's chromosome complement in preparation for sexual reproduction. This reduction in ploidy requires that in meiotic prophase, each pair of homologous chromosomes (homologs) identify one another and form physical links through DNA recombination. Here, we review recent advances in understanding the complex morphological changes that chromosomes undergo during meiotic prophase to promote homolog identification and crossing over. We focus on the structural maintenance of chromosomes (SMC) family cohesin complexes and the meiotic chromosome axis, which together organize chromosomes and promote recombination. We then discuss the architecture and dynamics of the conserved synaptonemal complex (SC), which assembles between homologs and mediates local and global feedback to ensure high fidelity in meiotic recombination. Finally, we discuss exciting new advances, including mechanisms for boosting recombination on particular chromosomes or chromosomal domains and the implications of a new liquid crystal model for SC assembly and structure. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Shugoshin is essential for meiotic prophase checkpoints in C. elegans

2018 ◽  
Author(s):  
Tisha Bohr ◽  
Christian R. Nelson ◽  
Stefani Giacopazzi ◽  
Piero Lamelza ◽  
Needhi Bhalla
Keyword(s):  
Sister Chromatid ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Chromosomal Protein ◽  
Loss Of Function ◽  
Chromosome Architecture ◽  
C Elegans ◽  
Meiotic Chromosomes ◽  
Chromatid Cohesion

AbstractThe conserved factor Shugoshin is dispensable in C. elegans for the two-step loss of sister chromatid cohesion that directs the proper segregation of meiotic chromosomes. We show that the C. elegans ortholog of Shugoshin, SGO-1, is required for checkpoint activity in meiotic prophase. This role in checkpoint function is similar to that of the meiotic chromosomal protein, HTP-3. Null sgo-1 mutants exhibit additional phenotypes similar to that of a partial loss of function allele of HTP-3: premature synaptonemal complex disassembly, the activation of alternate DNA repair pathways and an inability to recruit a conserved effector of the DNA damage pathway, HUS-1. SGO-1 localizes to pre-meiotic nuclei, when HTP-3 is present but not yet loaded onto chromosome axes, suggesting an early role in regulating meiotic chromosome metabolism. We propose that SGO-1 acts during pre-meiotic replication to ensure fully functional meiotic chromosome architecture, rendering these chromosomes competent for checkpoint activity and normal progression of meiotic recombination. Given that most research on Shugoshin has been focused on its regulation of sister chromatid cohesion in meiosis, this novel role may be conserved but previously uncharacterized in other organisms. Further, our findings expand the repertoire of Shugoshin’s functions beyond coordinating regulatory activities at the centromere.

scholarly journals DNA break formation induces Scc2/cohesin-dependent recruitment of condensin to meiotic chromosomes

2020 ◽  
Author(s):  
Tovah E. Markowitz ◽  
Jonna Heldrich ◽  
Andreas Hochwagen
Keyword(s):  
Chromosome Pairing ◽  
Meiotic Chromosome ◽  
Strand Break ◽  
Chromatin Loop ◽  
Loop Formation ◽  
Meiotic Chromosomes ◽  
Attachment Sites ◽  
Loop Dynamics ◽  
Structural Maintenance Of Chromosome ◽  
Break Formation

AbstractMeiotic chromosome pairing, recombination, and fertility depends on the conserved loop-axis architecture of meiotic chromosomes. This architecture is modulated by condensin, a structural maintenance of chromosome (SMC) complex that catalyzes chromatin loop formation. Here, we investigated how condensin is recruited to meiotic chromosomes in Saccharomyces cerevisiae. We show that double-strand-break (DSB) formation, the initiating event of meiotic recombination, causes condensin redistribution from the nucleolus to DSB hotspots, pericentromeric regions, and axis attachment sites. Hotspot association of condensin correlates weakly with break probability but does not depend on local DSB formation, whereas association with axis sites and pericentromeric regions depends on the Scc2-associated pool of cohesin, another SMC complex. Intriguingly, Scc2 distribution also changes in response to DSB formation. As condensin and Scc2-cohesin both catalyze chromatin loop extrusion, their redistribution upon DSB formation implies a profound change in chromatin loop dynamics that may help promote proper chromosome pairing and DNA repair.

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