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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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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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