title: PPARβ interprets a chromatin signature of pluripotency to promote embryonic differentiation at gastrulation.
abstract: Epigenetic post-transcriptional modifications of histone tails are thought to help in coordinating gene expression during development. An epigenetic signature is set in pluripotent cells and interpreted later at the onset of differentiation. In pluripotent cells, epigenetic marks normally associated with active genes (H3K4me3) and with silent genes (H3K27me3) atypically co-occupy chromatin regions surrounding the promoters of important developmental genes. However, it is unclear how these epigenetic marks are recognized when cell differentiation starts and what precise role they play. Here, we report the essential role of the nuclear receptor peroxisome proliferator-activated receptor β (PPARβ, NR1C2) in Xenopus laevis early development. By combining loss-of-function approaches, large throughput transcript expression analysis by the mean of RNA-seq and intensive chromatin immunoprecipitation experiments, we unveil an important cooperation between epigenetic marks and PPARβ. During Xenopus laevis gastrulation PPARβ recognizes H3K27me3 marks that have been deposited earlier at the pluripotent stage to activate early differentiation genes. Thus, PPARβis the first identified transcription factor that interprets an epigenetic signature of pluripotency, in vivo, during embryonic development. This work paves the way for a better mechanistic understanding of how the activation of hundreds of genes is coordinated during early development.
authors.affiliation: Center for Integrative Genomics, National Research Center "Frontiers in Genetics", University of Lausanne, Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rotman
authors.affiliation: Vital-IT group, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guex
authors.affiliation: Center for Integrative Genomics, National Research Center "Frontiers in Genetics", University of Lausanne, Lausanne, Switzerland.
authors.forename: Erwan
authors.initials: E
authors.lastname: Gouranton
authors.affiliation: Center for Integrative Genomics, National Research Center "Frontiers in Genetics", University of Lausanne, Lausanne, Switzerland ; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
authors.forename: Walter
authors.initials: W
authors.lastname: Wahli
mesh_terms: D000818:Animals; D001483:Base Sequence; D036703:Blastula / Q000166:cytology / Q000196:embryology; D002454:Cell Differentiation / Q000235:genetics*; D002843:Chromatin / Q000235:genetics*; D044127:Epigenesis, Genetic; D054262:Gastrulation / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D048068:PPAR-beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; D048068:PPAR-beta; D012333:RNA, Messenger; D008239:Lysine