Journal
SCIENCE
Volume 324, Issue 5935, Pages 1716-1719Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1172026
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Funding
- European Molecular Biology Organization Long Term Fellowship
- Medical Research Council [G0301153]
- Wellcome Trust Programme [065061/Z]
- MRC [G0301153] Funding Source: UKRI
- Medical Research Council [G0301153] Funding Source: researchfish
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In the central domain of fission yeast centromeres, the kinetochore is assembled on CENP-A(Cnp1) 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-AC(np1) 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-A(Cnp1) 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.
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