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

• Published in: Science (American Association for the Advancement of Science) Vol. 292; no. 5514; pp. 110 - 113
• Main Authors: Nakayama, Jun-ichi, Rice, Judd C., Strahl, Brian D., Allis, C. David, Shiv I. S. Grewal
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 06.04.2001; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Acetylation; Antibodies; Biochemistry; Biological and medical sciences; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Centromere - metabolism; Centromeres; Chromatin; Chromatin. Chromosome; Chromosomes, Fungal - metabolism; Clr4 protein; Epigenetics; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Silencing; Genes, Fungal; Genetic loci; Heterochromatin; Heterochromatin - metabolism; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; Histones; Histones - chemistry; Histones - metabolism; Insects; Life sciences; Lysine - metabolism; Methylation; Methyltransferases - chemistry; Methyltransferases - genetics; Methyltransferases - metabolism; Molecular and cellular biology; Molecular genetics; Mutation; Perceptual localization; Protein Methyltransferases; Protein Structure, Tertiary; Proteins; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Saccharomyces cerevisiae Proteins; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins; Swi6 protein; Transcription Factors - metabolism; Yeast; Yeasts; United States; Fungi; Chromatin; Molecular structure; Schizosaccharomyces pombe; Ascomycetes; Mutation; Methylation; Histone H3; Thallophyta
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1060118

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 Lys9methylation in vivo. Localization of Swi6, a homolog of Drosophila HP1, to heterochomatic regions is dependent on H3 Lys9methylation. Moreover, an H3-specific deacetylase Clr3 and a β-propeller domain protein Rik1 are required for H3 Lys9methylation 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.