Imprinting control regions (ICRs) are marked by mono-allelic bivalent chromatin when transcriptionally inactive

Stéphanie Maupetit-Méhouas (1) , Bertille Montibus , David Nury (2) , Chiharu Tayama , Michel M. Wassef (3) , Satya Kota (4) , Anne Fogli (5) , Fabiana Cerqueira campos , Kenichiro Hata (6) , Robert Feil (7) , Raphaël Margueron (8) , Kazuhiko Nakabayashi (6) , Franck Court (4) , Philippe P. Arnaud (9)

1 UCA [2017-2020] - Université Clermont Auvergne [2017-2020]
2 I-STEM - Institut des cellules souches pour le traitement et l'étude des maladies monogéniques
3 Hôpital Lariboisière, Department of Pathology, University of Paris 7 - Denis Diderot, Faculty of Medicine
4 IGMM - Institut de Génétique Moléculaire de Montpellier
5 Interactions génétiques et cellulaires au cours de la différenciation
6 Department of Maternal-Fetal Biology
7 Interfakultäres Institut für Biochemie
8 Endocrinologie moléculaire et cellulaire des cancers
9 GReD - Génétique, Reproduction et Développement

Parental allele-specific expression of imprinted genes is mediated by imprinting control regions (ICRs) that are constitutively marked by DNA methy-lation 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 lifespan. 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.

Domaines: Biologie moléculaire; Génomique, Transcriptomique et Protéomique [q-bio.GN]; Réseaux moléculaires [q-bio.MN]; Cancer

Stéphanie Maupetit-Méhouas, Bertille Montibus, David Nury, Chiharu Tayama, Michel M. Wassef, et al.. Imprinting control regions (ICRs) are marked by mono-allelic bivalent chromatin when transcriptionally inactive. Nucleic Acids Research, 2016, 44 (2), pp.621 - 635. ⟨10.1093/nar/gkv960⟩. ⟨hal-01917293⟩