Cohesin-interacting protein WAPL-1 regulates meiotic chromosome structure and cohesion by antagonizing specific cohesin complexes

Abstract

Wapl induces cohesin dissociation from DNA throughout the mitotic cell cycle, modulating sister chromatid cohesion and higher-order chromatin structure. Cohesin complexes containing meiosis-specific kleisin subunits govern most aspects of meiotic chromosome function, but whether Wapl regulates these complexes remains unknown. We show that during C. elegans oogenesis WAPL-1 antagonizes binding of cohesin containing COH-3/4 kleisins, but not REC-8, demonstrating that sensitivity to WAPL-1 is dictated by kleisin identity. By restricting the amount of chromosome-associated COH-3/4 cohesin, WAPL-1 controls chromosome structure throughout meiotic prophase. In the absence of REC-8, WAPL-1 inhibits COH-3/4-mediated cohesion, which requires crossover-fated events formed during meiotic recombination. Thus, WAPL-1 promotes functional specialization of meiotic cohesin: WAPL-1-sensitive COH-3/4 complexes modulate higher-order chromosome structure, while WAPL-1-refractory REC-8 complexes provide stable cohesion. Surprisingly, a WAPL-1-independent mechanism removes cohesin before metaphase I. Our studies provide insight into how meiosis-specific cohesin complexes are regulated to ensure formation of euploid gametes.DOI: http://dx.doi.org/10.7554/eLife.10851.001

Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse

“…During S phase, WAPL-PDS5B function is antagonized by Sororin, which displaces WAPL from PDS5B, thereby promoting cohesin loading and/or stabilization (Shintomi and Hirano, 2009; Zhang et al, 2008). Recent studies in Caenorhabditis elegans , Saccharomyces cerevisiae and Arabidopsis thaliana demonstrated a role for WAPL in cohesin regulation during meiosis (Challa et al, 2016; Crawley et al, 2016; De et al, 2014). In C. elegans oogenesis, WAPL-1 antagonizes binding of cohesin containing the COH-3/4 kleisins, but not REC-8, and promotes a WAPL-1-independent mechanism that removes cohesin before metaphase I (Crawley et al, 2016).…”

“…Recent studies in Caenorhabditis elegans , Saccharomyces cerevisiae and Arabidopsis thaliana demonstrated a role for WAPL in cohesin regulation during meiosis (Challa et al, 2016; Crawley et al, 2016; De et al, 2014). In C. elegans oogenesis, WAPL-1 antagonizes binding of cohesin containing the COH-3/4 kleisins, but not REC-8, and promotes a WAPL-1-independent mechanism that removes cohesin before metaphase I (Crawley et al, 2016). In S. Cerevisiae, the ortholog of WAPL (Rad61/Wpl1) negatively regulates chromosome axis compaction and is required for efficient resolution of telomere clustering during meiosis I (Challa et al, 2016).…”

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

“…The sharp drop of REC-8 molecules upon meiotic prophase entry does not depend on the presence of COH-3/4, as it occurs even in a coh-4 coh-3 mutant (FIG2S1B). Cohesin release factor WAPL-1 may play a role in REC-8 removal, as a drop in REC-8 levels upon meiotic entry is not observed in a wapl-1 mutant (FIG2S1B); however, interpretation of this finding is complicated by the fact that COH-3/4 cohesins load prematurely at low levels during S phase in the wapl-1 mutant (Crawley et al, 2016), so REC-8 may not be loaded at normal levels in this mutant.…”

“…During metazoan meiosis, chromosome axis organization and meiotic sister chromatid cohesion are mediated by at least two different cohesin complexes that contain distinct kleisin subunits and/or load at distinct times. Sister chromatid cohesion is mediated by complexes containing REC-8 in worms, REC8 in mammals and C(2)M in flies, whereas axis formation requires COH-3 and COH-4 in worms, REC8 and RAD21L in mammals and the SOLO-SUNN-containing cohesin complex in flies (Crawley et al, 2016;Gyuricza et al, 2016;Pasierbek et al, 2001;Severson et al, 2009;Xu et al, 2005).…”

“…Previous work provided evidence that REC-8 and COH-3/4 cohesin complexes play functionally distinct roles during C. elegans meiosis (Severson et al, 2009;Severson and Meyer, 2014): REC-8 has been demonstrated to mediate sister chromatid cohesion, whereas COH-3/4 plays a key role in axis organization (FIG2S1A). Further, these functionally distinct complexes differ in their timing of association with chromatin: REC-8 cohesins (like murine REC8) load during pre-meiotic DNA replication, whereas COH-3/4 cohesins (like murine RAD21L) load after completion of S phase, at the beginning of prophase ((for review: (Ishiguro, 2019)) and are insufficient to maintain connections between sister chromatids in the absence of recombination (Crawley et al, 2016). Our data support and extend these findings substantially in several ways.…”