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Science 4 January 2008:
Vol. 319. no. 5859, pp. 94 - 97
DOI: 10.1126/science.1150944
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Reports

Heterochromatin and RNAi Are Required to Establish CENP-A Chromatin at Centromeres

Hernan Diego Folco,1 Alison L. Pidoux,1 Takeshi Urano,2 Robin C. Allshire1*

Heterochromatin is defined by distinct posttranslational modifications on histones, such as methylation of histone H3 at lysine 9 (H3K9), which allows heterochromatin protein 1 (HP1)–related chromodomain proteins to bind. Heterochromatin is frequently found near CENP-A chromatin, which is the key determinant of kinetochore assembly. We have discovered that the RNA interference (RNAi)–directed heterochromatin flanking the central kinetochore domain at fission yeast centromeres is required to promote CENP-ACnp1 and kinetochore assembly over the central domain. The H3K9 methyltransferase Clr4 (Suv39); the ribonuclease Dicer, which cleaves heterochromatic double-stranded RNA to small interfering RNA (siRNA); Chp1, a component of the RNAi effector complex (RNA-induced initiation of transcriptional gene silencing; RITS); and Swi6 (HP1) are required to establish CENP-ACnp1 chromatin on naïve templates. Once assembled, CENP-ACnp1 chromatin is propagated by epigenetic means in the absence of heterochromatin. Thus, another, potentially conserved, role for centromeric RNAi-directed heterochromatin has been identified.

1 Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, 6.34 Swann Building, Edinburgh EH9 3JR, Scotland, UK.
2 Department of Biochemistry 2, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

* To whom correspondence should be addressed. E-mail: robin.allshire{at}ed.ac.uk

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Synthetic Heterochromatin Bypasses RNAi and Centromeric Repeats to Establish Functional Centromeres.
A. Kagansky, H. D. Folco, R. Almeida, A. L. Pidoux, A. Boukaba, F. Simmer, T. Urano, G. L. Hamilton, and R. C. Allshire (2009)
Science 324, 1716-1719
   Abstract »    Full Text »    PDF »
Diverse roles of HP1 proteins in heterochromatin assembly and functions in fission yeast.
T. Fischer, B. Cui, J. Dhakshnamoorthy, M. Zhou, C. Rubin, M. Zofall, T. D. Veenstra, and S. I. S. Grewal (2009)
PNAS 106, 8998-9003
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Active establishment of centromeric CENP-A chromatin by RSF complex.
M. Perpelescu, N. Nozaki, C. Obuse, H. Yang, and K. Yoda (2009)
J. Cell Biol. 185, 397-407
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Meiotic maturation failure induced by DICER1 deficiency is derived from primary oocyte ooplasm.
D. M Mattiske, L. Han, and J. R Mann (2009)
Reproduction 137, 625-632
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Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa.
Z. A. Lewis, S. Honda, T. K. Khlafallah, J. K. Jeffress, M. Freitag, F. Mohn, D. Schubeler, and E. U. Selker (2009)
Genome Res. 19, 427-437
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Splicing Factors Facilitate RNAi-Directed Silencing in Fission Yeast.
E. H. Bayne, M. Portoso, A. Kagansky, I. C. Kos-Braun, T. Urano, K. Ekwall, F. Alves, J. Rappsilber, and R. C. Allshire (2008)
Science 322, 602-606
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Heterochromatin Integrity Affects Chromosome Reorganization After Centromere Dysfunction.
K. Ishii, Y. Ogiyama, Y. Chikashige, S. Soejima, F. Masuda, T. Kakuma, Y. Hiraoka, and K. Takahashi (2008)
Science 321, 1088-1091
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The Eukaryotic Genome as an RNA Machine.
P. P. Amaral, M. E. Dinger, T. R. Mercer, and J. S. Mattick (2008)
Science 319, 1787-1789
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