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Originally published in Science Express on 15 March 2001
Science 6 April 2001:
Vol. 292. no. 5514, pp. 110 - 113
DOI: 10.1126/science.1060118
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Reports

Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly

Jun-ichi Nakayama,1 Judd C. Rice,2 Brian D. Strahl,2 C. David Allis,2 Shiv I. S. Grewal1*

The assembly of higher order chromatin structures has been linked to the covalent modifications of histone tails. We provide in vivo evidence that lysine 9 of histone H3 (H3 Lys9) is preferentially methylated by the Clr4 protein at heterochromatin-associated regions in fission yeast. Both the conserved chromo- and SET domains of Clr4 are required for H3 Lys9 methylation in vivo. Localization of Swi6, a homolog of Drosophila HP1, to heterochomatic regions is dependent on H3 Lys9 methylation. Moreover, an H3-specific deacetylase Clr3 and a beta -propeller domain protein Rik1 are required for H3 Lys9 methylation by Clr4 and Swi6 localization. These data define a conserved pathway wherein sequential histone modifications establish a "histone code" essential for the epigenetic inheritance of heterochromatin assembly.

1 Cold Spring Harbor Laboratory, Post Office Box 100, Cold Spring Harbor, NY 11724, USA.
2 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
*   To whom correspondence should be addressed. E-mail: grewal{at}cshl.org

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Cyclin D1 Inhibits Peroxisome Proliferator-activated Receptor {gamma}-mediated Adipogenesis through Histone Deacetylase Recruitment.
M. Fu, M. Rao, T. Bouras, C. Wang, K. Wu, X. Zhang, Z. Li, T.-P. Yao, and R. G. Pestell (2005)
J. Biol. Chem. 280, 16934-16941
   Abstract »    Full Text »    PDF »
Class II Histone Deacetylases: from Sequence to Function, Regulation, and Clinical Implication.
X.-J. Yang and S. Gregoire (2005)
Mol. Cell. Biol. 25, 2873-2884
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Relationship between Histone H3 Lysine 9 Methylation, Transcription Repression, and Heterochromatin Protein 1 Recruitment.
M. D. Stewart, J. Li, and J. Wong (2005)
Mol. Cell. Biol. 25, 2525-2538
   Abstract »    Full Text »    PDF »
Role of Protein Methylation in Regulation of Transcription.
D. Y. Lee, C. Teyssier, B. D. Strahl, and M. R. Stallcup (2005)
Endocr. Rev. 26, 147-170
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Ddb1 controls genome stability and meiosis in fission yeast.
C. Holmberg, O. Fleck, H. A. Hansen, C. Liu, R. Slaaby, A. M. Carr, and O. Nielsen (2005)
Genes & Dev. 19, 853-862
   Abstract »    Full Text »    PDF »
The role of heterochromatin in centromere function.
A. L Pidoux and R. C Allshire (2005)
Phil Trans R Soc B 360, 569-579
   Abstract »    Full Text »    PDF »
Conversion of DNA methyltransferases into azidonucleosidyl transferases via synthetic cofactors.
L. R. Comstock and S. R. Rajski (2005)
Nucleic Acids Res. 33, 1644-1652
   Abstract »    Full Text »    PDF »
Transcription Factor Interactions and Chromatin Modifications Associated with p53-Mediated, Developmental Repression of the Alpha-Fetoprotein Gene.
T. T. Nguyen, K. Cho, S. A. Stratton, and M. C. Barton (2005)
Mol. Cell. Biol. 25, 2147-2157
   Abstract »    Full Text »    PDF »
Epigenetic Regulation by Histone Methylation and Histone Variants.
P. Cheung and P. Lau (2005)
Mol. Endocrinol. 19, 563-573
   Abstract »    Full Text »    PDF »
Conserved Locus-Specific Silencing Functions of Schizosaccharomyces pombe sir2+.
L. L. Freeman-Cook, E. B. Gomez, E. J. Spedale, J. Marlett, S. L. Forsburg, L. Pillus, and P. Laurenson (2005)
Genetics 169, 1243-1260
   Abstract »    Full Text »    PDF »
Onset and inheritance of abnormal epigenetic regulation in hematopoietic cells.
S. Bottardi, V. Bourgoin, N. Pierre-Charles, and E. Milot (2005)
Hum. Mol. Genet. 14, 493-502
   Abstract »    Full Text »    PDF »


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