title: Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth.
abstract: The potential for early embryonic events to program epigenetic states that influence adult physiology remains an important question in health and development. Using the imprinted Zdbf2 locus as a paradigm for the early programming of phenotypes, we demonstrate here that chromatin changes that occur in the pluripotent embryo can be dispensable for embryogenesis but instead signal essential regulatory information in the adult. The Liz (long isoform of Zdbf2) transcript is transiently expressed in early embryos and embryonic stem cells (ESCs). This transcription locally promotes de novo DNA methylation upstream of the Zdbf2 promoter, which antagonizes Polycomb-mediated repression of Zdbf2. Strikingly, mouse embryos deficient for Liz develop normally but fail to activate Zdbf2 in the postnatal brain and show indelible growth reduction, implying a crucial role for a Liz-dependent epigenetic switch. This work provides evidence that transcription during an early embryonic timeframe can program a stable epigenetic state with later physiological consequences.
authors.affiliation: Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.
authors.forename: Maxim V C
authors.initials: MV
authors.lastname: Greenberg
authors.affiliation: Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.
authors.forename: Juliane
authors.initials: J
authors.lastname: Glaser
authors.affiliation: Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.
authors.forename: Máté
authors.initials: M
authors.lastname: Borsos
authors.affiliation: Institut Curie, CNRS, Paris, France.
authors.forename: Fatima El
authors.initials: FE
authors.lastname: Marjou
authors.affiliation: Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.
authors.forename: Marius
authors.initials: M
authors.lastname: Walter
authors.affiliation: Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.|École des Mines, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Teissandier
authors.affiliation: Institut Curie, PSL Research University, INSERM, CNRS, Paris, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Bourc'his
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D002843:Chromatin / Q000235:genetics; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D047108:Embryonic Development / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D057890:Epigenomics; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*
chemical_list: D002843:Chromatin; C000591279:GPR1 protein, mouse; D043562:Receptors, G-Protein-Coupled