title: Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6.
abstract: 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 approximately 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.
authors.affiliation: Department of Biochemistry, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Dover
authors.forename: Jessica
authors.initials: J
authors.lastname: Schneider
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Tawiah-Boateng
authors.forename: Adam
authors.initials: A
authors.lastname: Wood
authors.forename: Kimberly
authors.initials: K
authors.lastname: Dean
authors.forename: Mark
authors.initials: M
authors.lastname: Johnston
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
mesh_terms: D004275:DNA, Ribosomal / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism*; D008025:Ligases / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008954:Models, Biological; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes
chemical_list: D004275:DNA, Ribosomal; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases; D008239:Lysine