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Science 25 August 2006:
Vol. 313. no. 5790, pp. 1134 - 1137
DOI: 10.1126/science.1128813
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Reports

Argonaute Slicing Is Required for Heterochromatic Silencing and Spreading

Danielle V. Irvine,1* Mikel Zaratiegui,1* Niraj H. Tolia,1* Derek B. Goto,1{dagger} Daniel H. Chitwood,1,2 Matthew W. Vaughn,1 Leemor Joshua-Tor,1,2 Robert A. Martienssen1,2{ddagger}

Small interfering RNA (siRNA) guides dimethylation of histone H3 lysine-9 (H3K9me2) via the Argonaute and RNA-dependent RNA polymerase complexes, as well as base-pairing with either RNA or DNA. We show that Argonaute requires the conserved aspartate-aspartate-histidine motif for heterochromatic silencing and for ribonuclease H–like cleavage (slicing) of target messages complementary to siRNA. In the fission yeast Schizosaccharomyces pombe, heterochromatic repeats are transcribed by polymerase II. We show that H3K9me2 spreads into silent reporter genes when they are embedded within these transcripts and that spreading requires read-through transcription, as well as slicing by Argonaute. Thus, siRNA guides histone modification by basepairing interactions with RNA.

1 Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
2 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

* These authors contributed equally to this work.

{dagger} Present address: Laboratory for Nanosystems Physiology, Research Institute for Electronic Science, Hokkaido University, Sapporo, 060-0812, Japan.

{ddagger} To whom correspondence should be addressed. E-mail: martiens{at}cshl.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Chp1-Tas3 Interaction Is Required To Recruit RITS to Fission Yeast Centromeres and for Maintenance of Centromeric Heterochromatin.
J. L. DeBeauchamp, A. Moses, V. J. P. Noffsinger, D. L. Ulrich, G. Job, A. M. Kosinski, and J. F. Partridge (2008)
Mol. Cell. Biol. 28, 2154-2166
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The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members.
T. A. Farazi, S. A. Juranek, and T. Tuschl (2008)
Development 135, 1201-1214
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Repeat-associated siRNAs cause chromatin silencing of retrotransposons in the Drosophila melanogaster germline.
M. S. Klenov, S. A. Lavrov, A. D. Stolyarenko, S. S. Ryazansky, A. A. Aravin, T. Tuschl, and V. A. Gvozdev (2007)
Nucleic Acids Res.
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Promoter-associated RNA is required for RNA-directed transcriptional gene silencing in human cells.
J. Han, D. Kim, and K. V. Morris (2007)
PNAS 104, 12422-12427
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A new paradigm for developmental biology.
J. S. Mattick (2007)
J. Exp. Biol. 210, 1526-1547
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Interaction of Epe1 With the Heterochromatin Assembly Pathway in Schizosaccharomyces pombe.
S. Isaac, J. Walfridsson, T. Zohar, D. Lazar, T. Kahan, K. Ekwall, and A. Cohen (2007)
Genetics 175, 1549-1560
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)