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Identification of chromosome sequence motifs that mediate meiotic pairing and synapsis in C. elegans

Nature Cell Biology volume 11, pages 934–942 (2009)Cite this article

An Erratum to this article was published on 01 September 2009

Abstract

Caenorhabditis elegans chromosomes contain specialized regions called pairing centres, which mediate homologous pairing and synapsis during meiosis. Four related proteins, ZIM-1, 2, 3 and HIM-8, associate with these sites and are required for their essential functions. Here we show that short sequence elements enriched in the corresponding chromosome regions selectively recruit these proteins in vivo. In vitro analysis using SELEX indicates that the binding specificity of each protein arises from a combination of two zinc fingers and an adjacent domain. Insertion of a cluster of recruiting motifs into a chromosome lacking its endogenous pairing centre is sufficient to restore homologous pairing, synapsis, crossover recombination and segregation. These findings help to illuminate how chromosome sites mediate essential aspects of meiotic chromosome dynamics.

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Figure 1: The X chromosome pairing centre region.
Figure 2: ZIM/HIM-8 recruitment motifs.
Figure 3: Sequence-specific binding by ZIM-2, ZIM-3, and HIM-8 protein fragments.
Figure 4: ZIM/HIM-8 recruiting arrays associate with nuclear envelope components.
Figure 5: HIM-8 recruitment motifs are sufficient for pairing centre function.
Figure 6: ZIM/HIM-8 proteins can interchangeably support pairing centre function.

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Acknowledgements

This work was supported by an NSF Predoctoral Fellowship (C.M.P.) and by Burroughs Wellcome Career Award 1000950 and NIH R01 GM065591 (A.F.D.). We are grateful to Anne Villeneuve for SYP-1 antibodies, Barbara Meyer, Kevin Corbett and Ed Rebar for valuable suggestions, to members of the Meyer lab for assistance with the extrachromosomal array assay and to members of the Dernburg lab and anonymous referees for helpful comments on the manuscript.

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  1. Carolyn M. Phillips

    Present address: Current address: Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge St. CPZN-7250, Boston, MA 02114, USA.,

Authors and Affiliations

  1. Department of Molecular and Cell Biology, University of California, 470 Stanley Hall, MC 3220, Berkeley, 94720, CA, USA

    Carolyn M. Phillips, Jacqueline H. Chretien & Abby F. Dernburg

  2. Sangamo BioSciences, Pt. Richmond Tech Center, 501 Canal Blvd., Suite A100, Richmond, 94804, California, USA

    Xiangdong Meng, Lei Zhang & Fyodor D. Urnov

  3. Howard Hughes Medical Institute, 185 Cambridge St. CPZN-7250, Boston, 02114, MA, USA

    Jacqueline H. Chretien & Abby F. Dernburg

  4. Life Sciences Division, Lawrence Berkeley National Laboratory, 185 Cambridge St. CPZN-7250, Boston, 02114, MA, USA

    Abby F. Dernburg

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Contributions

C.M.P. and A.F.D. designed most experiments and wrote the manuscript. J.H.C. provided cDNA clones for the SELEX assays, which were executed by X.M. and L.Z. with guidance from F.D.U. All other experiments were performed by C.M.P.

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Correspondence to Abby F. Dernburg.

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Phillips, C., Meng, X., Zhang, L. et al. Identification of chromosome sequence motifs that mediate meiotic pairing and synapsis in C. elegans. Nat Cell Biol 11, 934–942 (2009). https://doi.org/10.1038/ncb1904

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