title: Pericentric heterochromatin generated by HP1 protein interaction-defective histone methyltransferase Suv39h1.
abstract: Pericentric regions form epigenetically organized silent heterochromatin structures that accumulate histone H3 lysine 9 trimethylation (H3K9me3) and HP1. At pericentric regions, Suv39h is the major enzyme that generates H3K9me3. Suv39h also interacts directly with HP1, a methylated H3K9-binding protein. However, it is not well characterized how HP1 interaction is important for Suv39h accumulation and Suv39h-mediated H3K9me3 formation at the pericentromere. To address this, we introduced the HP1 binding-defective N-terminally truncated mouse Suv39h1 (ΔN) into Suv39h-deficient embryonic stem cells. Interestingly, pericentric accumulation of ΔN and ΔN-mediated H3K9me3 was observed to recover, but HP1 accumulation was only marginally restored. ΔN also rescued DNA methyltransferase Dnmt3a and -3b accumulation and DNA methylation of the pericentromere. In contrast, other pericentric heterochromatin features, such as ATRX protein association and H4K20me3, were not recovered. Finally, derepressed major satellite repeats were partially silenced by ΔN expression. These findings clearly showed that the Suv39h-HP1 binding is dispensable for pericentric H3K9me3 and DNA methylation, but this interaction and HP1 recruitment/accumulation seem to be crucial for complete formation of heterochromatin.
authors.affiliation: From the Graduate School of Biostudies, Kyoto University, 53 Shogoin, Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan,; the Cellular Memory Laboratory, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Muramatsu
authors.affiliation: the Fächereverband Anatomie, Institut für Zell and Neurobiologie, Charite-Universitätmedizin, 10117 Berlin, Germany.
authors.forename: Prim B
authors.initials: PB
authors.lastname: Singh
authors.affiliation: the Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: From the Graduate School of Biostudies, Kyoto University, 53 Shogoin, Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan,; the Institute for Virus Research, Kyoto University, 53 Shogoin, Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan, and.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: the Cellular Memory Laboratory, RIKEN, Wako, Saitama 351-0198, Japan,; CREST (Core Research for Evolutional Science and Technology), Japan Science and Technology Agency, Kawaguchi 332-0012, Japan. Electronic address: yshinkai@riken.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shinkai
mesh_terms: D000818:Animals; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology*; D000090205:DNA Methyltransferase 3A; D053595:Embryonic Stem Cells; D057809:HEK293 Cells; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000075924:X-linked Nuclear Protein; D000097584:DNA Methyltransferase 3B
chemical_list: D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone; D004248:DNA (Cytosine-5-)-Methyltransferases; D004265:DNA Helicases; D000090205:DNA Methyltransferase 3A; D006570:Heterochromatin; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D008780:Methyltransferases; D009687:Nuclear Proteins; D012097:Repressor Proteins; D000075924:X-linked Nuclear Protein; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; C498700:Suv39h1 protein, mouse; C490462:Atrx protein, mouse
keywords: ATRX; Chromatin Structure; DNA Methylation; Dnmt3; HP1; Heterochromatin; Histone Methylation; Mammal; Suv39h