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An inverse relationship to germline transcription defines centromeric chromatin in C. elegans

Nature volume 484, pages 534–537 (2012)Cite this article

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Abstract

Centromeres are chromosomal loci that direct segregation of the genome during cell division. The histone H3 variant CENP-A (also known as CenH3) defines centromeres in monocentric organisms, which confine centromere activity to a discrete chromosomal region, and holocentric organisms, which distribute centromere activity along the chromosome length1,2,3. Because the highly repetitive DNA found at most centromeres is neither necessary nor sufficient for centromere function, stable inheritance of CENP-A nucleosomal chromatin is postulated to propagate centromere identity epigenetically4. Here, we show that in the holocentric nematode Caenorhabditis elegans pre-existing CENP-A nucleosomes are not necessary to guide recruitment of new CENP-A nucleosomes. This is indicated by lack of CENP-A transmission by sperm during fertilization and by removal and subsequent reloading of CENP-A during oogenic meiotic prophase. Genome-wide mapping of CENP-A location in embryos and quantification of CENP-A molecules in nuclei revealed that CENP-A is incorporated at low density in domains that cumulatively encompass half the genome. Embryonic CENP-A domains are established in a pattern inverse to regions that are transcribed in the germline and early embryo, and ectopic transcription of genes in a mutant germline altered the pattern of CENP-A incorporation in embryos. Furthermore, regions transcribed in the germline but not embryos fail to incorporate CENP-A throughout embryogenesis. We propose that germline transcription defines genomic regions that exclude CENP-A incorporation in progeny, and that zygotic transcription during early embryogenesis remodels and reinforces this basal pattern. These findings link centromere identity to transcription and shed light on the evolutionary plasticity of centromeres.

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Figure 1: CeCENP-A dynamics in meiotic prophase, at fertilization and across embryonic divisions.
Figure 2: Genome-wide mapping of CeCENP-A-enriched chromatin.
Figure 3: Relationship between CeCENP-A and gene expression.
Figure 4: Germline expression controls CeCENP-A occupancy in the progeny embryos.

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References

  1. Malik, H. S. & Henikoff, S. Major evolutionary transitions in centromere complexity. Cell 138, 1067–1082 (2009)

    Article  CAS  Google Scholar 

  2. Allshire, R. C. & Karpen, G. H. Epigenetic regulation of centromeric chromatin: old dogs, new tricks? Nature Rev. Genet. 9, 923–937 (2008)

    Article  CAS  Google Scholar 

  3. Choo, K. The Centromere (Ocford Univ. Press, 1997)

    Google Scholar 

  4. Sullivan, K. F. A solid foundation: functional specialization of centromeric chromatin. Curr. Opin. Genet. Dev. 11, 182–188 (2001)

    Article  CAS  Google Scholar 

  5. Shelby, R. D., Monier, K. & Sullivan, K. F. Chromatin assembly at kinetochores is uncoupled from DNA replication. J. Cell Biol. 151, 1113–1118 (2000)

    Article  CAS  Google Scholar 

  6. Jansen, L. E. T., Black, B. E., Foltz, D. R. & Cleveland, D. W. Propagation of centromeric chromatin requires exit from mitosis. J. Cell Biol. 176, 795–805 (2007)

    Article  CAS  Google Scholar 

  7. Schuh, M., Lehner, C. F. & Heidmann, S. Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase. Curr. Biol. 17, 237–243 (2007)

    Article  CAS  Google Scholar 

  8. Monen, J., Maddox, P. S., Hyndman, F., Oegema, K. & Desai, A. Differential role of CENP-A in the segregation of holocentric C. elegans chromosomes during meiosis and mitosis. Nature Cell Biol. 7, 1248–1255 (2005)

    Article  Google Scholar 

  9. Liu, T. et al. Broad chromosomal domains of histone modification patterns in C. elegans . Genome Res. 21, 227–236 (2011)

    Article  CAS  Google Scholar 

  10. Seydoux, G. & Dunn, M. A. Transcriptionally repressed germ cells lack a subpopulation of phosphorylated RNA polymerase II in early embryos of Caenorhabditis elegans and Drosophila melanogaster . Development 124, 2191–2201 (1997)

    CAS  PubMed  Google Scholar 

  11. Baugh, L. R., Hill, A. A., Slonim, D. K., Brown, E. L. & Hunter, C. P. Composition and dynamics of the Caenorhabditis elegans early embryonic transcriptome. Development 130, 889–900 (2003)

    Article  CAS  Google Scholar 

  12. Edgar, L. G., Wolf, N. & Wood, W. B. Early transcription in Caenorhabditis elegans embryos. Development 120, 443–451 (1994)

    CAS  PubMed  Google Scholar 

  13. Rechtsteiner, A. et al. The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny. PLoS Genet. 6, e1001091 (2010)

    Article  Google Scholar 

  14. Andersen, E. C. & Horvitz, H. R. Two C. elegans histone methyltransferases repress lin-3 EGF transcription to inhibit vulval development. Development 134, 2991–2999 (2007)

    Article  CAS  Google Scholar 

  15. Claycomb, J. M. et al. The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation. Cell 139, 123–134 (2009)

    Article  CAS  Google Scholar 

  16. van Wolfswinkel, J. C. et al. CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs. Cell 139, 135–148 (2009)

    Article  CAS  Google Scholar 

  17. Ravi, M. et al. Meiosis-specific loading of the centromere-specific histone CENH3 in Arabidopsis thaliana . PLoS Genet. 7, e1002121 (2011)

    Article  CAS  Google Scholar 

  18. Lomiento, M., Jiang, Z., D’Addabbo, P., Eichler, E. E. & Rocchi, M. Evolutionary-new centromeres preferentially emerge within gene deserts. Genome Biol. 9, R173 (2008)

    Article  Google Scholar 

  19. Piras, F. M. et al. Uncoupling of satellite DNA and centromeric function in the genus Equus . PLoS Genet. 6, e1000845 (2010)

    Article  Google Scholar 

  20. Warburton, P. E. Chromosomal dynamics of human neocentromere formation. Chromosome Res. 12, 617–626 (2004)

    Article  CAS  Google Scholar 

  21. Oegema, K., Desai, A., Rybina, S., Kirkham, M. & Hyman, A. A. Functional analysis of kinetochore assembly in Caenorhabditis elegans . J. Cell Biol. 153, 1209–1226 (2001)

    Article  CAS  Google Scholar 

  22. Maddox, P. S., Hyndman, F., Monen, J., Oegema, K. & Desai, A. Functional genomics identifies a Myb domain-containing protein family required for assembly of CENP-A chromatin. J. Cell Biol. 176, 757–763 (2007)

    Article  CAS  Google Scholar 

  23. Frøkjær-Jensen, C. et al. Single-copy insertion of transgenes in Caenorhabditis elegans . Nature Genet. 40, 1375–1383 (2008)

    Article  Google Scholar 

  24. Dammermann, A. et al. Centriole assembly requires both centriolar and pericentriolar material proteins. Dev. Cell 7, 815–829 (2004)

    Article  CAS  Google Scholar 

  25. Cheeseman, I. M. et al. A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension. Genes Dev. 18, 2255–2268 (2004)

    Article  CAS  Google Scholar 

  26. Edgar, L. G. Blastomere culture and analysis. Methods Cell Biol. 48, 303–321 (1995)

    Article  CAS  Google Scholar 

  27. Wang, X. et al. Identification of genes expressed in the hermaphrodite germ line of C. elegans using SAGE. BMC Genomics 10, 213 (2009)

    Article  Google Scholar 

  28. Meissner, B. et al. An integrated strategy to study muscle development and myofilament structure in Caenorhabditis elegans . PLoS Genet. 5, e1000537 (2009)

    Article  Google Scholar 

  29. Kolasinska-Zwierz, P. et al. Differential chromatin marking of introns and expressed exons by H3K36me3. Nature Genet. 41, 376–381 (2009)

    Article  CAS  Google Scholar 

  30. Reinke, V., Gil, I. S., Ward, S. & Kazmer, K. Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans . Development 131, 311–323 (2004)

    Article  CAS  Google Scholar 

  31. Smyth, G. K. Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 3, Article3 (2004)

    Article  MathSciNet  Google Scholar 

  32. Storey, J. D. & Tibshirani, R. Statistical significance for genomewide studies. Proc. Natl Acad. Sci. USA 100, 9440–9445 (2003)

    Article  ADS  MathSciNet  CAS  Google Scholar 

  33. Bolstad, B. M., Irizarry, R. A., Astrand, M. & Speed, T. P. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19, 185–193 (2003)

    Article  CAS  Google Scholar 

  34. Irizarry, R. A. et al. Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res. 31, e15 (2003)

    Article  Google Scholar 

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Acknowledgements

We thank S. Ward for the purified sperm sample, M. Gupta for help with analysis, J. Ahringer for advice on fixation and ChIP procedures, and A. Dernburg and other members of the Lieb modENCODE group for helpful discussions. This work was supported by a modENCODE grant (U01 HG004270), and by grants from NIH to A.D. (GM074215 and ARRA supplement) and S.S. (GM34059). R.G. was supported by a fellowship from the National Science Foundation of Switzerland. L.G. was supported by NIH T32 GM008646. A.D. and K.O. receive salary and other support from the Ludwig Institute for Cancer Research.

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Author notes

  1. Karen W. Yuen, Francie Barron, Paul Maddox, Anthony Essex & Joost Monen

    Present address: Present addresses: School of Biological Sciences, the University of Hong Kong, Pokfulam, Hong Kong (K.W.Y.); Department of Craniofacial Biology, University of Colorado, Health Sciences Center, Aurora, Colorado 80045, USA (F.B.); Institute for Research in Immunology and Cancer, Department of Pathology and Cell Biology, University of Montreal, Montreal, Quebec H3C 3J7, Canada (P.M.); The Salk Institute for Biological Studies, San Diego, California 92186, USA (A.E.); Department of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853, USA (J.M.).,

  2. Reto Gassmann, Andreas Rechtsteiner and Karen W. Yuen: These authors contributed equally to this work.

Authors and Affiliations

  1. Ludwig Institute for Cancer Research and Department of Cellular & Molecular Medicine University of California San Diego, La Jolla, 92037, California, USA

    Reto Gassmann, Karen W. Yuen, Andrew Muroyama, Francie Barron, Paul Maddox, Anthony Essex, Joost Monen, Karen Oegema & Arshad Desai

  2. Department of Molecular Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, 95064, California, USA

    Andreas Rechtsteiner, Thea Egelhofer, Laura Gaydos & Susan Strome

  3. Department of Biology, Carolina Center for Genome Sciences and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, 27599, North Carolina, USA

    Sevinc Ercan & Jason D. Lieb

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Contributions

R.G., A.M. and T.E. performed ChIP experiments; A.R. performed analysis of all ChIP-chip datasets with advice from S.S.; K.W.Y. performed the photobleaching and α-amanitin experiments; F.B. and P.M. performed the mating inheritance experiment, analysed replication-independence and measured CeCENP-A levels in sperm; R.G. performed GFP–CeCENP-A localization analysis, quantified CeCENP-A levels in nuclei with K.W.Y., and performed qPCR on germline RNA provided by L.G.; A.E., A.M. and J.M. generated GFP–CeCENP-A strains; S.E. and J.D.L. helped initiate ChIP analysis of CeCENP-A; K.O. and A.D. made initial observations that established the project; A.D., R.G., A.R., K.W.Y. and S.S. prepared the figures and wrote the paper with advice from J.D.L. and K.O.; A.D. and S.S. supervised the project.

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Correspondence to Susan Strome or Arshad Desai.

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The authors declare no competing financial interests.

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Gassmann, R., Rechtsteiner, A., Yuen, K. et al. An inverse relationship to germline transcription defines centromeric chromatin in C. elegans. Nature 484, 534–537 (2012). https://doi.org/10.1038/nature10973

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