title: Imprinting control regions (ICRs) are marked by mono-allelic bivalent chromatin when transcriptionally inactive.
abstract: Parental allele-specific expression of imprinted genes is mediated by imprinting control regions (ICRs) that are constitutively marked by DNA methylation imprints on the maternal or paternal allele. Mono-allelic DNA methylation is strictly required for the process of imprinting and has to be faithfully maintained during the entire life-span. While the regulation of DNA methylation itself is well understood, the mechanisms whereby the opposite allele remains unmethylated are unclear. Here, we show that in the mouse, at maternally methylated ICRs, the paternal allele, which is constitutively associated with H3K4me2/3, is marked by default by H3K27me3 when these ICRs are transcriptionally inactive, leading to the formation of a bivalent chromatin signature. Our data suggest that at ICRs, chromatin bivalency has a protective role by ensuring that DNA on the paternal allele remains unmethylated and protected against spurious and unscheduled gene expression. Moreover, they provide the proof of concept that, beside pluripotent cells, chromatin bivalency is the default state of transcriptionally inactive CpG island promoters, regardless of the developmental stage, thereby contributing to protect cell identity.
authors.affiliation: CNRS, UMR6293, F-63001 Clermont-Ferrand, France Inserm, U1103, 63001 Clermont-Ferrand, France Université Clermont Auvergne, Laboratoire GReD, BP 10448, 63000 Clermont-Ferrand, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Maupetit-Méhouas
authors.affiliation: CNRS, UMR6293, F-63001 Clermont-Ferrand, France Inserm, U1103, 63001 Clermont-Ferrand, France Université Clermont Auvergne, Laboratoire GReD, BP 10448, 63000 Clermont-Ferrand, France.
authors.forename: Bertille
authors.initials: B
authors.lastname: Montibus
authors.affiliation: CNRS, UMR6293, F-63001 Clermont-Ferrand, France Inserm, U1103, 63001 Clermont-Ferrand, France Université Clermont Auvergne, Laboratoire GReD, BP 10448, 63000 Clermont-Ferrand, France.
authors.forename: David
authors.initials: D
authors.lastname: Nury
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tayama
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Wassef
authors.affiliation: Institute of Molecular Genetics, CNRS UMR-5535 and University of Montpellier, 1919 route de Mende, 34293 Montpellier, France.
authors.forename: Satya K
authors.initials: SK
authors.lastname: Kota
authors.affiliation: CNRS, UMR6293, F-63001 Clermont-Ferrand, France Inserm, U1103, 63001 Clermont-Ferrand, France Université Clermont Auvergne, Laboratoire GReD, BP 10448, 63000 Clermont-Ferrand, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Fogli
authors.affiliation: CNRS, UMR6293, F-63001 Clermont-Ferrand, France Inserm, U1103, 63001 Clermont-Ferrand, France Université Clermont Auvergne, Laboratoire GReD, BP 10448, 63000 Clermont-Ferrand, France.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Cerqueira Campos
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
authors.affiliation: Institute of Molecular Genetics, CNRS UMR-5535 and University of Montpellier, 1919 route de Mende, 34293 Montpellier, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.affiliation: Institut Curie, 26 Rue d'Ulm, 75005 Paris, France; INSERM U934, 26 Rue d'Ulm, 75005 Paris, France; CNRS UMR3215, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Margueron
authors.affiliation: Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.affiliation: CNRS, UMR6293, F-63001 Clermont-Ferrand, France Inserm, U1103, 63001 Clermont-Ferrand, France Université Clermont Auvergne, Laboratoire GReD, BP 10448, 63000 Clermont-Ferrand, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Court
authors.affiliation: CNRS, UMR6293, F-63001 Clermont-Ferrand, France Inserm, U1103, 63001 Clermont-Ferrand, France Université Clermont Auvergne, Laboratoire GReD, BP 10448, 63000 Clermont-Ferrand, France philippe.arnaud@udamail.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Arnaud
mesh_terms: D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009928:Organ Specificity; D011401:Promoter Regions, Genetic
chemical_list: D002843:Chromatin; C498796:Dnmt3l protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases