title: Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins.
abstract: Polycomb group (PcG) proteins form multimeric chromatin-associated protein complexes that are involved in heritable repression of gene activity. Two distinct human PcG complexes have been characterized. The EED/EZH2 PcG complex utilizes histone deacetylation to repress gene activity. The HPC/HPH PcG complex contains the HPH, RING1, BMI1, and HPC proteins. Here we show that vertebrate Polycomb homologs HPC2 and XPc2, but not M33/MPc1, interact with the histone lysine methyltransferase (HMTase) SUV39H1 both in vitro and in vivo. We further find that overexpression of SUV39H1 induces selective nuclear relocalization of HPC/HPH PcG proteins but not of the EED/EZH2 PcG proteins. This SUV39H1-dependent relocalization concentrates the HPC/HPH PcG proteins to the large pericentromeric heterochromatin domains (1q12) on human chromosome 1. Within these PcG domains we observe increased H3-K9 methylation. Finally, we show that H3-K9 HMTase activity is associated with endogenous HPC2. Our findings suggest a role for the SUV39H1 HMTase and histone H3-K9 methylation in the targeting of human HPC/HPH PcG proteins to modified chromatin structures.
authors.affiliation: Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, Plantage Muidergracht 12, 1018 TV Amsterdam, The Netherlands.
authors.forename: Richard G A B
authors.initials: RG
authors.lastname: Sewalt
authors.forename: Monika
authors.initials: M
authors.lastname: Lachner
authors.forename: Mark
authors.initials: M
authors.lastname: Vargas
authors.forename: Karien M
authors.initials: KM
authors.lastname: Hamer
authors.forename: Jan L
authors.initials: JL
authors.lastname: den Blaauwen
authors.forename: Thijs
authors.initials: T
authors.lastname: Hendrix
authors.forename: Martin
authors.initials: M
authors.lastname: Melcher
authors.forename: Dieter
authors.initials: D
authors.lastname: Schweizer
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
authors.forename: Arie P
authors.initials: AP
authors.lastname: Otte
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002503:Centromere / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism*; D002878:Chromosomes, Human, Pair 1 / Q000378:metabolism; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008025:Ligases; D046911:Macromolecular Substances; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D063146:Polycomb-Group Proteins; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases
chemical_list: D006657:Histones; D046911:Macromolecular Substances; D063146:Polycomb-Group Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C407843:SUV39H1 protein, human; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; C570427:CBX4 protein, human