Abstract
During meiotic prophase, cohesin complexes mediate cohesion between sister chromatids and promote pairing and synapsis of homologous chromosomes. Precisely how the activity of cohesin is controlled to promote these events is not fully understood. In metazoans, cohesion establishment between sister chromatids during mitotic divisions is accompanied by recruitment of the cohesion-stabilizing protein Sororin. During somatic cell division cycles, Sororin is recruited in response to DNA replication-dependent modification of the cohesin complex by ESCO acetyltransferases. How Sororin is recruited and acts in meiosis is less clear. Here, we have surveyed the chromosomal localization of Sororin and its relationship to the meiotic cohesins and other chromatin modifiers with the objective of determining how Sororin contributes to meiotic chromosome dynamics. We show that Sororin localizes to the cores of meiotic chromosomes in a manner that is dependent on synapsis and the synaptonemal complex protein SYCP1. In contrast, cohesin, with which Sororin interacts in mitotic cells, shows axial enrichment on meiotic chromosomes even in the absence of synapsis between homologs. Using high-resolution microscopy, we show that Sororin is localized to the central region of the synaptonemal complex. These results indicate that Sororin regulation during meiosis is distinct from its regulation in mitotic cells and may suggest that it interacts with a distinctly different partner to ensure proper chromosome dynamics in meiosis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- SC:
-
Synaptonemal complex
- SA:
-
Stromal antigen
- AE:
-
Axial element
- LE:
-
Lateral element
References
Agostinho A, Manneberg O, van Schendel R et al (2016) High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation. EMBO Rep 17:901–913. doi:10.15252/embr.201642030
Bannister LA, Reinholdt LG, Munroe RJ, Schimenti JC (2004) Positional cloning and characterization of mouse mei8, a disrupted allelle of the meiotic cohesin Rec8. Genesis 40:184–194. doi:10.1002/gene.20085
Bisig CG, Guiraldelli MF, Kouznetsova A et al (2012) Synaptonemal complex components persist at centromeres and are required for homologous centromere pairing in mouse spermatocytes. PLoS Genet 8:e1002701. doi:10.1371/journal.pgen.1002701
Biswas U, Wetzker C, Lange J et al (2013) Meiotic cohesin SMC1β provides prophase I centromeric cohesion and is required for multiple synapsis-associated functions. PLoS Genet 9:e1003985. doi:10.1371/journal.pgen.1003985.s012
Cahoon CK, Hawley RS (2016) Regulating the construction and demolition of the synaptonemal complex. Nat Publ Group 23:369–377. doi:10.1038/nsmb.3208
Costa Y, Speed R, Ollinger R et al (2005) Two novel proteins recruited by synaptonemal complex protein 1 (SYCP1) are at the centre of meiosis. J Cell Sci 118:2755–2762. doi:10.1242/jcs.02402
de Vries FAT (2005) Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination, and XY body formation. Genes Dev 19:1376–1389. doi:10.1101/gad.329705
Dobson MJ, Pearlman RE, Karaiskakis A et al (1994) Synaptonemal complex proteins: occurrence, epitope mapping and chromosome disjunction. J Cell Sci 107(Pt 10):2749–2760
Eijpe M, Heyting C, Gross B, Jessberger R (2000) Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes. J Cell Sci 113(Pt 4):673–682
Eijpe M, Offenberg H, Jessberger R et al (2003) Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1beta and SMC3. J Cell Biol 160:657–670. doi:10.1083/jcb.200212080
Fraune J, Schramm S, Alsheimer M, Benavente R (2012) The mammalian synaptonemal complex: protein components, assembly and role in meiotic recombination. Exp Cell Res 318:1340–1346. doi:10.1016/j.yexcr.2012.02.018
Fukuda T, Daniel K, Wojtasz L et al (2010) A novel mammalian HORMA domain-containing protein, HORMAD1, preferentially associates with unsynapsed meiotic chromosomes. Exp Cell Res 316:158–171. doi:10.1016/j.yexcr.2009.08.007
Fukuda T, Fukuda N, Agostinho A et al (2014) STAG3-mediated stabilization of REC8 cohesin complexes promotes chromosome synapsis during meiosis. EMBO J 33:1243–1255. doi:10.1002/embj.201387329
Fukuda T, Höög C (2010) The mouse cohesin-associated protein PDS5B is expressed in testicular cells and is associated with the meiotic chromosome axes. Genes (Basel) 1:484–494. doi:10.3390/genes1030484
Gandhi R, Gillespie PJ, Hirano T (2006) Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase. Curr Biol 16:2406–2417. doi:10.1016/j.cub.2006.10.061
Gerlich D, Koch B, Dupeux F et al (2006) Live-cell imaging reveals a stable cohesin-chromatin interaction after but not before DNA replication. Curr Biol 16:1571–1578. doi:10.1016/j.cub.2006.06.068
Gómez R, Felipe-Medina N, Ruiz-Torres M et al (2016) Sororin loads to the synaptonemal complex central region independently of meiotic cohesin complexes. EMBO Rep 17:695–707. doi:10.15252/embr.201541060
Gutiérrez-Caballero C, Herrán Y, Sánchez-Martín M et al (2011) Identification and molecular characterization of the mammalian α-kleisin RAD21L. Cell Cycle 10:1477–1487
Hamer G, Wang H, Bolcun-Filas E et al (2008) Progression of meiotic recombination requires structural maturation of the central element of the synaptonemal complex. J Cell Sci 121:2445–2451. doi:10.1242/jcs.033233
Handel MA, Schimenti JC (2010) Genetics of mammalian meiosis: regulation, dynamics and impact on fertility. Nat Rev Genet 11:124–136. doi:10.1038/nrg2723
Herrán Y, Gutiérrez-Caballero C, Sánchez-Martín M et al (2011) The cohesin subunit RAD21L functions in meiotic synapsis and exhibits sexual dimorphism in fertility. EMBO J 30:3091–3105. doi:10.1038/emboj.2011.222
Hopkins J, Hwang G, Jacob J et al (2014) Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes. PLoS Genet 10:e1004413. doi:10.1371/journal.pgen.1004413
Hunter N (2015) Meiotic recombination: the essence of heredity. Cold Spring Harb Perspect Biol. doi:10.1101/cshperspect.a016618
Ishiguro K-I, Kim J, Fujiyama-Nakamura S et al (2011) A new meiosis-specific cohesin complex implicated in the cohesin code for homologous pairing. EMBO Rep 12:267–275. doi:10.1038/embor.2011.2
Jin H, Guacci V, H-G Y (2009) Pds5 is required for homologue pairing and inhibits synapsis of sister chromatids during yeast meiosis. J Cell Biol 186:713–725. doi:10.1083/jcb.200810107
Kagami A, Sakuno T, Yamagishi Y et al (2011) Acetylation regulates monopolar attachment at multiple levels during meiosis I in fission yeast. EMBO Rep 12:1189–1195. doi:10.1038/embor.2011.188
Kolas NK, Yuan L, Höög C et al (2004) Male mouse meiotic chromosome cores deficient in structural proteins SYCP3 and SYCP2 align by homology but fail to synapse and have possible impaired specificity of chromatin loop attachment. Cytogenet Genome Res 105:182–188. doi:10.1159/000078188
Kueng S, Hegemann B, Peters BH et al (2006) Wapl controls the dynamic association of cohesin with chromatin. Cell 127:955–967. doi:10.1016/j.cell.2006.09.040
Lafont AL, Song J, Rankin S (2010) Sororin cooperates with the acetyltransferase Eco2 to ensure DNA replication-dependent sister chromatid cohesion. Proc Natl Acad Sci U S A 107:20364–20369. doi:10.1073/pnas.1011069107
Lammers JH, Offenberg HH, van Aalderen M et al (1994) The gene encoding a major component of the lateral elements of synaptonemal complexes of the rat is related to X-linked lymphocyte-regulated genes. Mol Cell Biol 14:1137–1146
Lee J, Hirano T (2011) RAD21L, a novel cohesin subunit implicated in linking homologous chromosomes in mammalian meiosis. J Cell Biol 192:263–276. doi:10.1083/jcb.201008005
Lee J, Iwai T, Yokota T, Yamashita M (2003) Temporally and spatially selective loss of Rec8 protein from meiotic chromosomes during mammalian meiosis. J Cell Sci 116:2781–2790. doi:10.1242/jcs.00495
Liu H, Rankin S, Yu H (2012) Phosphorylation-enabled binding of SGO1-PP2A to cohesin protects sororin and centromeric cohesion during mitosis. Nat Cell Biol 15:40–49. doi:10.1038/ncb2637
Meuwissen RL, Offenberg HH, Dietrich AJ et al (1992) A coiled-coil related protein specific for synapsed regions of meiotic prophase chromosomes. EMBO J 11:5091–5100
Méndez J, Stillman B (2000) Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol Cell Biol 20:8602–8612
Nasmyth K, Haering CH (2009) Cohesin: its roles and mechanisms. Annu Rev Genet 43:525–558. doi:10.1146/annurev-genet-102108-134233
Nishiyama T, Ladurner R, Schmitz J et al (2010) Sororin mediates sister chromatid cohesion by antagonizing Wapl. Cell 143:737–749. doi:10.1016/j.cell.2010.10.031
Novak I, Wang H, Revenkova E et al (2008) Cohesin Smc1beta determines meiotic chromatin axis loop organization. J Cell Biol 180:83–90. doi:10.1083/jcb.200706136
Offenberg HH, Schalk JA, Meuwissen RL et al (1998) SCP2: a major protein component of the axial elements of synaptonemal complexes of the rat. Nucleic Acids Res 26:2572–2579
Ouyang Z, Zheng G, Tomchick DR et al (2016) Structural basis and IP6 requirement for Pds5-dependent cohesin dynamics. Mol Cell 62:248–259. doi:10.1016/j.molcel.2016.02.033
Parra MT, Viera A, Gómez R et al (2004) Involvement of the cohesin Rad21 and SCP3 in monopolar attachment of sister kinetochores during mouse meiosis I. J Cell Sci 117:1221–1234. doi:10.1242/jcs.00947
Pelttari J, Hoja MR, Yuan L et al (2001) A meiotic chromosomal core consisting of cohesin complex proteins recruits DNA recombination proteins and promotes synapsis in the absence of an axial element in mammalian meiotic cells. Mol Cell Biol 21:5667–5677. doi:10.1128/MCB.21.16.5667-5677.2001
Peters AH, Plug AW, van Vugt MJ, de Boer P (1997) A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chromosom Res 5:66–68
Pezzi N, Prieto I, Kremer L et al (2000) STAG3, a novel gene encoding a protein involved in meiotic chromosome pairing and location of STAG3-related genes flanking the Williams-Beuren syndrome deletion. FASEB J 14:581–592
Prieto I, Suja JA, Pezzi N et al (2001) Mammalian STAG3 is a cohesin specific to sister chromatid arms in meiosis I. Nat Cell Biol 3:761–766. doi:10.1038/35087082
Qiao H, Chen JK, Reynolds A et al (2012) Interplay between synaptonemal complex, homologous recombination, and centromeres during mammalian meiosis. PLoS Genet 8:e1002790. doi:10.1371/journal.pgen.1002790
Rankin S (2015) Complex elaboration: making sense of meiotic cohesin dynamics. FEBS J. doi:10.1111/febs.13301
Rankin S, Ayad NG, Kirschner MW (2005) Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates. Mol Cell 18:185–200. doi:10.1016/j.molcel.2005.03.017
Revenkova E, Eijpe M, Heyting C et al (2004) Cohesin SMC1β is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination. Nat Cell Biol 6:555–562. doi:10.1038/ncb1135
Schramm S, Fraune J, Naumann R et al (2011) A novel mouse synaptonemal complex protein is essential for loading of central element proteins, recombination, and fertility. PLoS Genet 7:e1002088. doi:10.1371/journal.pgen.1002088
Severson AF, Meyer BJ (2014) Divergent kleisin subunits of cohesin specify mechanisms to tether and release meiotic chromosomes. Elife 3:e03467. doi: 10.7554/eLife.03467
Song J, Lafont A, Chen J et al (2012) Cohesin acetylation promotes sister chromatid cohesion only in association with the replication machinery. J Biol Chem. doi:10.1074/jbc.M112.400192
Sumara I, Vorlaufer E, Gieffers C et al (2000) Characterization of vertebrate cohesin complexes and their regulation in prophase. J Cell Biol 151:749–762
Ward A, Hopkins J, Mckay M et al (2016) Genetic interactions between the meiosis-specific cohesin components, STAG3, REC8, and RAD21L. G3 (Bethesda) 6:1713–1724. doi:10.1534/g3.116.029462
Winters T, McNicoll F, Jessberger R (2014) Meiotic cohesin STAG3 is required for chromosome axis formation and sister chromatid cohesion. EMBO J 33:1256–1270. doi:10.1002/embj.201387330
Wu FM, Nguyen JV, Rankin S (2011) A conserved motif at the C terminus of sororin is required for sister chromatid cohesion. J Biol Chem 286:3579–3586. doi:10.1074/jbc.M110.196758
Xu H, Beasley M, Verschoor S et al (2004) A new role for the mitotic RAD21/SCC1 cohesin in meiotic chromosome cohesion and segregation in the mouse. EMBO Rep 5:378–384. doi:10.1038/sj.embor.7400121
Xu H, Beasley MD, Warren WD et al (2005) Absence of mouse REC8 cohesin promotes synapsis of sister chromatids in meiosis. Dev Cell 8:949–961. doi:10.1016/j.devcel.2005.03.018
Yuan L, Liu JG, Zhao J et al (2000) The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell 5:73–83
Zhang B, Jain S, Song H et al (2007) Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome. Development 134:3191–3201. doi:10.1242/dev.005884
Zhang Z, Ren Q, Yang H et al (2005) Budding yeast PDS5 plays an important role in meiosis and is required for sister chromatid cohesion. Mol Microbiol 56:670–680. doi:10.1111/j.1365-2958.2005.04582.x
Acknowledgements
We are grateful to Christer Hoog for providing the Sycp1 mutant mouse, John Schimenti for providing Sycp3 and Rec8 mutant mice, and Dean Dawson for careful review of the manuscript. We are also grateful the excellent technical support of Ben Fowler and Julie Crane of the OMRF Imaging Core in the collection of 3D SIM images. The OMX super resolution microscope was recently purchased with the generous support of the Oklahoma Center for Adult Stem Cell Research. This work was supported by National Institutes of Health grants GM117155 and HD069458 to P.W.J., GM103636 to R.J.P., GM101250 to S.R. and March of Dimes research grant FY14-256 to R.J.P. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Ethics statement
All mice were bred at Johns Hopkins University (JHU, Baltimore, MD) or at Oklahoma Medical Research Foundation (OMRF, Oklahoma City, OK) under standard conditions in accordance with the National Institutes of Health and the US Department of Agriculture criteria, and protocols for their care and use were approved by the Institutional Animal Care and Use Committees (IACUC) of JHU and OMRF.
Additional information
Responsible Editor: Beth A Sullivan
Electronic supplementary material
ESM 1
(TIFF 487 kb)
Rights and permissions
About this article
Cite this article
Jordan, P.W., Eyster, C., Chen, J. et al. Sororin is enriched at the central region of synapsed meiotic chromosomes. Chromosome Res 25, 115–128 (2017). https://doi.org/10.1007/s10577-016-9542-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10577-016-9542-8