title: A glue for heterochromatin maintenance: stable SUV39H1 binding to heterochromatin is reinforced by the SET domain.
abstract: Trimethylation of histone H3 lysine 9 and the subsequent binding of heterochromatin protein 1 (HP1) mediate the formation and maintenance of pericentromeric heterochromatin. Trimethylation of H3K9 is governed by the histone methyltransferase SUV39H1. Recent studies of HP1 dynamics revealed that HP1 is not a stable component of heterochromatin but is highly mobile (Cheutin, T., A.J. McNairn, T. Jenuwein, D.M. Gilbert, P.B. Singh, and T. Misteli. 2003. Science. 299:721-725; Festenstein, R., S.N. Pagakis, K. Hiragami, D. Lyon, A. Verreault, B. Sekkali, and D. Kioussis. 2003. Science. 299:719-721). Because the mechanism by which SUV39H1 is recruited to and interacts with heterochromatin is unknown, we studied the dynamic properties of SUV39H1 in living cells by using fluorescence recovery after photobleaching and fluorescence resonance energy transfer. Our results show that a substantial population of SUV39H1 is immobile at pericentromeric heterochromatin, suggesting that, in addition to its catalytic activity, SUV39H1 may also play a structural role at pericentromeric regions. Analysis of SUV39H1 deletion mutants indicated that the SET domain mediates this stable binding. Furthermore, our data suggest that the recruitment of SUV39H1 to heterochromatin is at least partly independent from that of HP1 and that HP1 transiently interacts with SUV39H1 at heterochromatin.
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, 2333 AL, Leiden, Netherlands.
authors.forename: Ilke M
authors.initials: IM
authors.lastname: Krouwels
authors.forename: Karien
authors.initials: K
authors.lastname: Wiesmeijer
authors.forename: Tsion E
authors.initials: TE
authors.lastname: Abraham
authors.forename: Chris
authors.initials: C
authors.lastname: Molenaar
authors.forename: Nico P
authors.initials: NP
authors.lastname: Verwoerd
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Tanke
authors.forename: Roeland W
authors.initials: RW
authors.lastname: Dirks
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002384:Catalysis / Q000187:drug effects; D045744:Cell Line, Tumor; D002503:Centromere / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D036681:Fluorescence Recovery After Photobleaching; D031541:Fluorescence Resonance Energy Transfer; D006570:Heterochromatin / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D041681:NIH 3T3 Cells; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008164:Luminescent Proteins; D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C054562:yellow fluorescent protein, Bacteria; D000090266:Chromobox Protein Homolog 5; C012589:trichostatin A; C407843:SUV39H1 protein, human; D008780:Methyltransferases