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Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin

Nature Structural & Molecular Biology volume 11, pages 1076–1083 (2004)Cite this article

Abstract

Post-translational histone modifications regulate epigenetic switching between different chromatin states. Distinct histone modifications, such as acetylation, methylation and phosphorylation, define different functional chromatin domains, and often do so in a combinatorial fashion. The centromere is a unique chromosomal locus that mediates multiple segregation functions, including kinetochore formation, spindle-mediated movements, sister cohesion and a mitotic checkpoint. Centromeric (CEN) chromatin is embedded in heterochromatin and contains blocks of histone H3 nucleosomes interspersed with blocks of CENP-A nucleosomes, the histone H3 variant that provides a structural and functional foundation for the kinetochore. Here, we demonstrate that the spectrum of histone modifications present in human and Drosophila melanogaster CEN chromatin is distinct from that of both euchromatin and flanking heterochromatin. We speculate that this distinct modification pattern contributes to the unique domain organization and three-dimensional structure of centromeric regions, and/or to the epigenetic information that determines centromere identity.

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Figure 1: H3 is not di- or trimethylated at Lys9 in CEN chromatin.
Figure 2: Quantification of overlap between histone modifications and CENP-A/CID on chromatin fibers from flies and humans.
Figure 3: H3 is not di- or trimethylated at Lys9 in CEN chromatin at metaphase.
Figure 4: Quantification of overlap between histone modifications and CENP-A/CID on metaphase chromosomes from humans and flies.
Figure 5: H3 and H4 are hypoacetylated in CEN chromatin.
Figure 6: H3 is dimethylated at Lys4 in CEN chromatin.
Figure 7: H3 is not trimethylated at Lys4 in CEN chromatin.
Figure 8: Model for three-dimensional organization of centromeric (CEN) chromatin in D. melanogaster and humans.

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Acknowledgements

We thank A. Skora for technical assistance, and K. Scott, C. Vaziri, A. Dernburg, D. Allis, S. Erhardt and C. Yan for discussions and advice. We acknowledge K. Maggert for originally coining the term “centro-chromatin.” We are indebted to T. Jenuwein and A. Peters for use of their unique H3 Lys9-triMe antibodies. This work was supported by the following grants: US Department of Energy LDRD 366987 and US National Institutes of Health (NIH) R01 GM66272 (G.H.K.), and American Cancer Society IRG-72-001-29 and NIH R01 GM069514 (B.A.S.).

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  1. Beth A Sullivan

    Present address: Department of Genetics and Genomics, Boston University School of Medicine, 715 Albany Street, E645, Boston, Massachusetts, 02118, USA

  2. Gary H Karpen

    Present address: Department of Genome Biology, Lawrence Berkeley National Lab and Department of Molecular and Cell Biology, University of California, Berkeley, One Cyclotron Road, Mail Stop 84R0171, Berkeley, California, 94720, USA

Authors and Affiliations

  1. Molecular and Cell Biology Laboratory, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, 92037, California, USA

    Beth A Sullivan & Gary H Karpen

  2. Department of Genetics and Genomics, Boston University School of Medicine, 715 Albany Street, E645, Boston, Massachusetts, 02118, USA

    Gary H Karpen

  3. Department of Genome Biology, Lawrence Berkeley National Lab and Department of Molecular and Cell Biology, University of California, Berkeley, One Cyclotron Road, Mail Stop 84R0171, Berkeley, California, 94720, USA

    Beth A Sullivan

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Correspondence to Beth A Sullivan.

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Sullivan, B., Karpen, G. Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin. Nat Struct Mol Biol 11, 1076–1083 (2004). https://doi.org/10.1038/nsmb845

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