Synthetic Heterochromatin Bypasses RNAi and Centromeric Repeats to Establish Functional Centromeres

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Science  26 Jun 2009:
Vol. 324, Issue 5935, pp. 1716-1719
DOI: 10.1126/science.1172026

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Synthetic Centromere

Every eukaryotic chromosome must have a centromere where the cell division machinery latches onto each chromosome pair to ensure an even apportioning of the genetic material between daughter cells. The characteristic (but not conserved) repeat sequences associated with most centromeres are thought to be required to induce an RNA interference (RNAi) response and thereby promote the formation of heterochromatin, needed for centromere function. Kagansky et al. (p. 1716) now show in fission yeast that these outer repeat sequences can be replaced in their entirety by very short sequences that recruit an enzyme, Clr4, which promotes the formation of heterochromatin in the absence of RNAi. Thus, flanking heterochromatin, regardless of its derivation, is all that is required for the formation of a functional centromere.


In the central domain of fission yeast centromeres, the kinetochore is assembled on CENP-ACnp1 nucleosomes. Normally, small interfering RNAs generated from flanking outer repeat transcripts direct histone H3 lysine 9 methyltransferase Clr4 to homologous loci to form heterochromatin. Outer repeats, RNA interference (RNAi), and centromeric heterochromatin are required to establish CENP-ACnp1 chromatin. We demonstrated that tethering Clr4 via DNA-binding sites at euchromatic loci induces heterochromatin assembly, with or without active RNAi. This synthetic heterochromatin completely substitutes for outer repeats on plasmid-based minichromosomes, promoting de novo CENP-ACnp1 and kinetochore assembly, to allow their mitotic segregation, even with RNAi inactive. Thus, the role of outer repeats in centromere establishment is simply the provision of RNAi substrates to direct heterochromatin formation; H3K9 methylation-dependent heterochromatin is alone sufficient to form functional centromeres.

  • * These authors contributed equally to this work.

  • Present Address: Ludwig Institute for Cancer Research, Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0660, USA.

  • Present Address: Laboratory of Cancer Epigenetics, Faculty of Medicine, Free University of Brussels, 808 route de Lennik, 1070 Brussels, Belgium.

  • § Present Address: Department of Molecular Biology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.

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