title: Polycomb repressive complex 2 and H3K27me3 cooperate with H3K9 methylation to maintain heterochromatin protein 1α at chromatin.
abstract: Methylation of histone H3 on lysine 9 or 27 is crucial for heterochromatin formation. Previously considered hallmarks of, respectively, constitutive and facultative heterochromatin, recent evidence has accumulated in favor of coexistence of these two marks and their cooperation in gene silencing maintenance. H3K9me2/3 ensures anchorage at chromatin of heterochromatin protein 1α (HP1α), a main component of heterochromatin. HP1α chromoshadow domain, involved in dimerization and interaction with partners, has additional but still unclear roles in HP1α recruitment to chromatin. Because of previously suggested links between polycomb repressive complex 2 (PRC2), which catalyzes H3K27 methylation, and HP1α, we tested whether PRC2 may regulate HP1α abundance at chromatin. We found that the EZH2 and SUZ12 subunits of PRC2 are required for HP1α stability, as knockdown of either protein led to HP1α degradation. Similar results were obtained upon overexpression of H3K27me2/3 demethylases. We further showed that binding of HP1α/β/γ to H3K9me3 peptides is greatly increased in the presence of H3K27me3, and this is dependent on PRC2. These data fit with recent proteomic studies identifying PRC2 as an indirect H3K9me3 binder in mouse tissues and suggest the existence of a cooperative mechanism of HP1α anchorage at chromatin involving H3 methylation on both K9 and K27 residues.
authors.affiliation: Genetic and Epigenetic Alterations of Genomes, de Duve Institute, Catholic University of Louvain, Brussels, Belgium.
authors.forename: Joanna
authors.initials: J
authors.lastname: Boros
authors.affiliation: Genetic and Epigenetic Alterations of Genomes, de Duve Institute, Catholic University of Louvain, Brussels, Belgium.
authors.forename: Nausica
authors.initials: N
authors.lastname: Arnoult
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, and de Duve Institute, Catholic University of Louvain, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Stroobant
authors.affiliation: WELBIO and de Duve Institute, Catholic University of Louvain, Brussels, Belgium.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Collet
authors.affiliation: Genetic and Epigenetic Alterations of Genomes, de Duve Institute, Catholic University of Louvain, Brussels, Belgium anabelle.decottignies@uclouvain.be.
authors.forename: Anabelle
authors.initials: A
authors.lastname: Decottignies
mesh_terms: D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability
chemical_list: C000715594:CBX5 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D000090266:Chromobox Protein Homolog 5; D063151:Polycomb Repressive Complex 2; D046988:Proteasome Endopeptidase Complex