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J. Biol. Chem., Vol. 277, Issue 32, 28368-28371, August 9, 2002
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From the § Department of Biochemistry, Saint Louis
University School of Medicine, St. Louis, Missouri 63104 and the
The DNA of eukaryotes is wrapped around
nucleosomes and packaged into chromatin. Covalent modifications of the
histone proteins that comprise the nucleosome alter chromatin structure
and have major effects on gene expression. Methylation of lysine 4 of
histone H3 by COMPASS is required for silencing of genes located near chromosome telomeres and within the rDNA (Krogan, N. J, Dover, J.,
Khorrami, S., Greenblatt, J. F., Schneider, J., Johnston, M., and
Shilatifard, A. (2002) J. Biol. Chem. 277, 10753-10755; Briggs, S. D., Bryk, M., Strahl, B. D., Cheung,
W. L., Davie, J. K., Dent, S. Y., Winston, F., and
Allis, C. D. (2001) Genes. Dev. 15, 3286-3295). To
learn about the mechanism of histone methylation, we surveyed the
genome of the yeast Saccharomyces cerevisiae for genes
necessary for this process. By analyzing ~4800 mutant
strains, each deleted for a different non-essential gene, we discovered that the ubiquitin-conjugating enzyme Rad6 is required for methylation of lysine 4 of histone H3. Ubiquitination of histone H2B on lysine 123 is the signal for the methylation of histone H3, which leads to
silencing of genes located near telomeres.
ACCELERATED PUBLICATION
Methylation of Histone H3 by COMPASS Requires Ubiquitination
of Histone H2B by Rad6*
,, and Department of Genetics, Washington University School of
Medicine, St. Louis, Missouri 63110
*
This work was supported in part by American Cancer Society
Grant RP69921801, National Institutes of Health Grant 1R01CA089455, and
a Mallinckrodt Foundation Award (to A. S.) and by funds from the James
S. McDonnell Foundation (to M. J.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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