title: Redundant mechanisms to form silent chromatin at pericentromeric regions rely on BEND3 and DNA methylation.
abstract: Constitutive heterochromatin is typically defined by high levels of DNA methylation and H3 lysine 9 trimethylation (H3K9Me3), whereas facultative heterochromatin displays DNA hypomethylation and high H3 lysine 27 trimethylation (H3K27Me3). The two chromatin types generally do not coexist at the same loci, suggesting mutual exclusivity. During development or in cancer, pericentromeric regions can adopt either epigenetic state, but the switching mechanism is unknown. We used a quantitative locus purification method to characterize changes in pericentromeric chromatin-associated proteins in mouse embryonic stem cells deficient for either the methyltransferases required for DNA methylation or H3K9Me3. DNA methylation controls heterochromatin architecture and inhibits Polycomb recruitment. BEND3, a protein enriched on pericentromeric chromatin in the absence of DNA methylation or H3K9Me3, allows Polycomb recruitment and H3K27Me3, resulting in a redundant pathway to generate repressive chromatin. This suggests that BEND3 is a key factor in mediating a switch from constitutive to facultative heterochromatin.
authors.affiliation: INSERM AVENIR, Institute of Human Genetics CNRS UPR1142, 141 rue de la Cardonille, 34000 Montpellier, France.
authors.forename: Nehmé
authors.initials: N
authors.lastname: Saksouk
authors.affiliation: Munich Centre of Integrated Protein Science and Adolf Butenandt Institute, Group, Ludwig-Maximillians University of Munich, Schillerstrasse 44, 80336 Munich, Germany.
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Barth
authors.affiliation: Institute of Genetics and Molecular and Cellular Biology (IGBMC), 1 rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Ziegler-Birling
authors.affiliation: The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Nelly
authors.initials: N
authors.lastname: Olova
authors.affiliation: INSERM AVENIR, Institute of Human Genetics CNRS UPR1142, 141 rue de la Cardonille, 34000 Montpellier, France.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Nowak
authors.affiliation: INSERM AVENIR, Institute of Human Genetics CNRS UPR1142, 141 rue de la Cardonille, 34000 Montpellier, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Rey
authors.affiliation: INSERM AVENIR, Institute of Human Genetics CNRS UPR1142, 141 rue de la Cardonille, 34000 Montpellier, France.
authors.forename: Julio
authors.initials: J
authors.lastname: Mateos-Langerak
authors.affiliation: Functional Proteomics Facility, Institute of Functional Genomics, 141 rue de la Cardonille, 34000 Montpellier, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Urbach
authors.affiliation: The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK; Epigenetics Programme, The Babraham Institute, Cambridge, CB22 3AT, UK; Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Wolf
authors.initials: W
authors.lastname: Reik
authors.affiliation: Institute of Genetics and Molecular and Cellular Biology (IGBMC), 1 rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Torres-Padilla
authors.affiliation: Munich Centre of Integrated Protein Science and Adolf Butenandt Institute, Group, Ludwig-Maximillians University of Munich, Schillerstrasse 44, 80336 Munich, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Imhof
authors.affiliation: INSERM AVENIR, Institute of Human Genetics CNRS UPR1142, 141 rue de la Cardonille, 34000 Montpellier, France. Electronic address: jerome.dejardin@igh.cnrs.fr.
authors.forename: Jérome
authors.initials: J
authors.lastname: Déjardin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Simboeck
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002503:Centromere / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000502:physiology; D020868:Gene Silencing; D056426:Genetic Loci; D006570:Heterochromatin / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018895:Microsatellite Repeats; D009687:Nuclear Proteins / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D012097:Repressor Proteins; D044767:Ubiquitin-Protein Ligases; D000097584:DNA Methyltransferase 3B
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D006657:Histones; D009687:Nuclear Proteins; D020543:Proteome; D012097:Repressor Proteins; D044767:Ubiquitin-Protein Ligases; D000097584:DNA Methyltransferase 3B; C000595575:BEND3 protein, mouse; C117054:Uhrf1 protein, mouse