Borek and Marston Genome Biology (2018) 19:134 https://doi.org/10.1186/s13059-018-1527-9

MEETINGREPORT Open Access Diverse model systems reveal common principles of Weronika E. Borek and Adele L. Marston*

Abstract super-enhancers during the mitosis-to-meiosis transition. Working in budding yeast, Gloria Brar (University of A meeting report on the 14th Gordon Research California, Berkeley, Berkeley, CA) provided insights Conference on Meiosis, held at Colby Sawyer College, into the surprising ‘sloppiness’ of the and New London, NH, USA, 9–15 June 2018, chaired by translation regulation throughout meiosis, in which Monica Colaiacovo, Harvard Medical School. cells ensure protein homeostasis of members of protein complexes by degradation, despite being capable of syn- thesizing components of protein complexes at stoichio- Introduction metric levels. Meiosis is a special type of that generates gametes. The production of viable gametes relies on complex maneuverings of the genome that happen in Insights into meiotic structure the context of cellular differentiation events that vary be- A key feature of meiosis is the pairing and of tween organism and sex. The meeting, entitled ‘Molecu- homologous . The lar mechanisms and regulation of meiosis across species’, (SC) is a conserved structure consisting of two lateral el- discussed new advances stemming from studies on a ements, a central element and transverse filaments that range of model organisms. Here, we highlight the major span the other elements to ‘zipper’ the homologs to- themes that emerged. We apologize to the presenters of gether. Although first visualized in 1956 by electron mi- the many excellent talks that are not featured due to croscopy, the molecular details of its workings have only space restrictions. just begun to be uncovered. Kevin Corbett (Ludwig In- stitute for Cancer Research, San Diego, CA) described Initiation and regulation of the meiotic the structural conservation of lateral element proteins differentiation program such as budding yeast Red1, human SYCP2-SYCP3, and Exciting advances in understanding the signals that in- Arabidopsis ASY3 and ASY4. In contrast to the long-held duce mouse male meiosis were presented. David Page view of the SC as a static structure, Abby Dernburg (Uni- (Whitehead Institute for Biomedical Research, Cambridge, versity of California, Berkeley, CA) demonstrated that dif- MA) revealed the global role of the STRA8 protein, ferent SC complex components show distinct diffusive long known to be stimulated at meiotic entry, in up- behavior in , leading to a model for regulating a meiotic transcriptional program consist- the spatial patterning of crossovers (CO). Sean Burgess ing of meiosis-specific and cell-cycle genes, whereas (University of California, Davis, CA) discussed the behav- Kei-ichiro Ishiguro (Institute of Molecular Embryology ior of the SC in a novel meiotic model, Danio rerio,where and , Kumamoto, Japan) identified a potential its assembly begins at telomeres. Amy MacQueen upstream regulator of STRA8, called MEIOSIN. Satoshi (Wesleyan University, Middletown, CT) showed separ- Namekawa (University of Cincinnati College of Medicine, able roles of the budding yeast SC protein Zip1 in Cincinnati, OH) disclosed the dynamic landscape of chromosome synapsis and CO formation. The unique structure of meiotic chromosomes was also the theme of Matt Neale’s (University of Sussex, Brighton, UK) talk, which revealed the first genome-wide chromo- some conformation capture (Hi-C) picture of early mei- * Correspondence: [email protected] Wellcome Centre , Institute of Cell Biology, School of Biological otic chromosomes from budding yeast. The appearance Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK of multiple pachytene-specific interactions was

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indicative of the axis-loop structures formed at this work on the newly discovered Zip3 homologs, stage, and dependent on axis proteins, including Vilya, Narya, and Nenya, and their roles in DSB and CO cohesin. formation. Gerry Smith (Fred Hutchinson Cancer Re- search Center, Seattle, WA) discussed the role of linear Regulating double strand break formation element proteins (that are related to the SC in other Meiotic recombination is initiated by the introduction of species) in limiting the number of DSBs by clustering hot- deliberate double strand breaks (DSBs) by the topoisom- spots in Schizosaccharomyces pombe, thus providing a mo- erase VI-related protein Spo11. DSBs are not randomly lecular basis for CO interference. Denise Zickler (Institute distributed, but are concentrated at preferred regions, of Integrative Cell Biology (I2BC), Gif-sur-Yvette, France) called hotspots. The past few years have seen an advance elucidated the roles of Sordaria macrospora Zip2 and Zip4 in our understanding of the chromosomal features that proteins in CO formation. Nancy Kleckner (Harvard typify hotspots. A collective highlight of the meeting was University, Cambridge, MA), in collaboration with the the progress made in understanding the connections be- Wang-Zhang laboratory (Shandong University, Jinan, tween DSB formation, the chromosome axis, and synapsis. China), observed that organisms vary their CO levels Scott Keeney (Memorial Sloan Kettering Cancer Center, onaper-nucleusbasis,andthattheydosobyvarying New York, NY) and Attila Tóth (Technical University of their chromosome axis length. She suggested that this Dresden, Dresden, Germany) both presented fascinating effect results from global modulation of chromatin loop work on the mouse pseudautosomal region. This small re- sizes. This variation leads to a broad distribution of the gion of homology between the X and Y chromosomes is numbers of COs per nucleus, and might be a mechan- necessary for their synapsis (and thus, meiosis) and under- ism to reconcile the opposing effects of recombination, goes high frequency DSB formation, but how this is as- which can both create evolutionarily favorable allele sured was not known. These two labs identified a novel combinations and disrupt existing combinations that meiotic protein that is required for DSB formation and have been selected to be favorable over time. Indeed, as synapsis at this region. Jesus Page (Universidad Autónoma revealed by Neil Hunter (University of California, Davis, de Madrid, Madrid, Spain) focused on the evolution, and Davis, CA) talking about SUMO-modifications in meiosis, surprising divergence, of sex chromosomes in non-model changes in axis length affect CO number in mice. mammals such as African pigmy mice. In addition to locus-specific regulation, meiotic recom- New technologies advancing our understanding bination is globally controlled. Maria Jasin (Memorial of meiosis Sloan Kettering Cancer Center, New York, NY) described Recent technologies relying on high-throughput sequen- how the ATM checkpoint kinase regulates DSB numbers cing have revolutionized our understanding of recom- and proximity in mouse spermatocytes. Enrique (Fadri) bination outcomes and their molecular mechanisms. Martinez-Perez (Imperial College, London, UK) postu- Expanding on ‘calibrated chromatin immunoprecipita- lated that in C. elegans, cohesins may regulate the kin- tion (ChIP)’, developed in the Nasmyth lab (University of ase CHK-2 in pachytene through the SC. Needhi Bhalla Oxford, Oxford, UK), Andreas Hochwagen (New York (University of California, Santa Cruz, CA) explained how University, New York, NY) introduced SNP-ChIP, in the C. elegans PCH-2 ATPase inhibits multiple meiotic which he used single nucleotide polymorphisms (SNPs) processes through the effector HORMA domain proteins. between diverged Saccharomyces cerevisiae strains to identify the spiked-in DNA used for calibration after se- Assuring crossovers quencing. Franz Klein (University of Vienna, Vienna, Meiotic recombination not only increases genetic diversity Austria) showed a similar calibration method, but used but also, critically, generates the crossover products that SNPs between different species, S. cerevisiae and S. constitute linkages between homologous chromosomes. kudriavzevii. Both strategies now allow calibration be- Ultimately, recombination must ensure sufficient and ap- tween samples from ChIP of meiosis-specific, untagged propriately placed COs to join every homolog pair prop- proteins. Franz Klein also devised Protec-Seq to map erly. Francesca Cole (University of Texas MD Anderson double-stranded DNA fragments that are protected by Cancer Center, Smithville, TX) used an elegant method to Spo11, which result from the unexpected occurrence obtain highly synchronized spermatocytes and to map of coordinated pairs of DSBs. Dan Camerini-Otero COs and non-crossovers and the time of their appearance, (National Institute of Diabetes and Digestive and Kidney leading to key predictions about the mechanism of DSB Diseases, Bethesda, MD) developed an elegant method to repair and CO assurance. The role of the CO factor, map replication origins in mouse testes and correlated the SUMO/ubiquitin ligase, Zip3, in meiosis is only beginning usage of DSB hotspots to early replicating domains. Mi- to be understood. Scott Hawley (Stowers Institute for chael Lichten (National Cancer Institute, Bethesda, MD) Medical Research, Kansas City, MO) presented beautiful employed a synthetic recombination hot-spot with evenly Borek and Marston Genome Biology (2018) 19:134 Page 3 of 3

and densely spaced SNPs together with high-throughput mitochondrial segregation and inheritance. Soni Lacefield sequencing to map parental strand contributions to meiotic (Indiana University, Bloomington, IN) entertained the recombinants. The analysis, performed in a mismatch- audience with beautiful videos of budding yeast mutants repair mutant background to preserve mismatches, re- that continue to divide after meiosis II, and was congratu- vealed the unexpected complexity of meiotic recombination lated by a questioner on her discovery of ‘Meiosis III’. outcomes. For example, template switching was found to be surprisingly common, whereas simple synthesis- Conclusions and perspectives dependent strand annealing was infrequent. In addition, A future challenge for the field is to apply our increas- novel methods that were not sequencing-based were ing molecular knowledge of meiosis in model systems also developed. Melina Schuh (Max Planck Institute for to reveal the origin of aneuploidy in human gametes. Biophysical Chemistry, Göttingen, Germany) described Although the scarcity of research material has prohib- a newly developed method, TrimAway, that allows the ited this in the past, partnerships between scientists rapid degradation of protein in oocytes in vivo. Barbara and in vitro fertilization clinics are beginning to address Meyer (University of California, Berkeley, Berkeley, CA), this issue, as discussed by Eva Hoffmann (University of who was presented with the Thomas Hunt Morgan Medal Copenhagen, Copenhagen, Denmark) at the meeting. by the Genetics Society of America for lifetime achieve- These future challenges will be addressed during the ment in genetics by Anne Villeneuve (Stanford University next GRC Meiosis meeting in 2020, which will be chaired School of Medicine, Stanford, CA) during the meeting, by Paula Cohen (Cornell University, Ithaca, NY) and outlined strategies for using CRISPR/Cas9 in C. elegans. co-chaired by Jeff Sekelsky (University of North Carolina, Chapel Hill, NC). Unique features of the meiotic cell cycle and Overall, this meeting showcased how a remarkable di- cytoskeleton versity in research topics and model systems enrich the Historically, the meiosis field has focused largely on field of meiosis and provided the ideal setting for com- meiotic recombination, leaving vast areas of meiotic mon principles to emerge. cell biology unexplored. This meeting highlighted the Abbreviations increased interest in some of the unusual aspects of ChIP: Chromatin immunoprecipitation; CO: Crossover; DSB: Double strand meiosis. Roberto Pezza (University of Oklahoma Health break; RPM: Rapid prophase movement; SC: Synaptonemal complex; Science Center, Oklahoma City, OK) discussed proteins SNP: Single nucleotide polymorphism that are required for the telomere-led rapid prophase Funding movements (RPMs) of chromosomes, an essential process We are grateful to Wellcome for funding awarded through a Senior Research occurring in meiotic prophase that helps to establish Fellowship to ALM (award number 107827) and through funding for the Wellcome Centre Cell biology (award number 203149). homologue interaction during pairing. Owen Davies (Newcastle University, Newcastle, UK) presented a crystal Authors’ contributions structure of the human MAJIN-TERB2 complex, eluci- WEB and ALM wrote the manuscript based on their notes from the meeting. – WEB and ALM gratefully acknowledge our colleagues cited herein for helpful dating the molecular basis of telomere nuclear enve- comments and suggestions. Both authors read and approved the final lope interactions, which facilitate RPMs. Hiro Ohkura manuscript. (University of Edinburgh, Edinburgh, UK) identified a Competing interests new pathway for nucleation in meiosis I The authors declare that they have no competing interests. Drosophila oocytes requiring the kinesin Subito, which compensates for the absence of major microtubule or- Publisher’sNote ganizers—centrosomes. Tomoya Kitajima (RIKEN Cen- Springer Nature remains neutral with regard to jurisdictional claims in ter for Biosystems Dynamics Research, Kobe, Japan) published maps and institutional affiliations. showed unexpected roles of kinetochore subcomplexes in the assembly of the meiosis I, but not the meiosis II, spindle in mouse oocytes. Sadie Wignall (Northwestern University, Evanston, IL) discussed the kinetochore- independent of C. elegans oo- cytes and explained how SUMOylation promotes the assembly of the ring complex that compensates for ki- netochores in this system. Raphael Mercier (Université Paris-Saclay, Versailles, France) identified a key cell cycle regulator in Arabidopsis that is important for chromo- some segregation. Elçin Ünal (University of California, Berkeley, Berkeley, CA) presented unexpected findings on