1. Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency
- Author
-
Edward Curry, Véronique Azuara, King Hang T. Mau, Roshni A. de Souza, Vincent Brochard, Alice Jouneau, Rute A. Tomaz, Luc Jouneau, Wout Megchelenbrink, Emma Bell, Hendrik Marks, Yaser Atlasi, Hendrik G. Stunnenberg, Bell, Emma [0000-0003-4103-3741], Tomaz, Rute A [0000-0002-9377-1431], Marks, Hendrik [0000-0002-4198-3731], Stunnenberg, Hendrik G [0000-0002-0066-1576], Azuara, Véronique [0000-0003-4608-3713], Apollo - University of Cambridge Repository, Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Imperial College London, Radboud Institute for Molecular Life Sciences (RIMLS), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Medical Research Council (MRC), Genesis Research Trust, The Portuguese Science & Technology foundation (FCT), Hammersmith Hospital, Faculty of Medicine and Health, Institute of Reproductive Sciences (IRS), Imperial College, London, Princess Máxima Center for Pediatric Oncology, Centre for Molecular Oncology, Department of Precision Medicine, Università della Campania Luigi Vanvitelli, Université Paris Saclay (COMUE), Institute of Reproductive and Developmental Biology, Faculty of Medicine, Department of Molecular Biology, Princeton University, Faculty of Health, Medicine and Life Sciences, Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), French Society for Stem Cell Research. Corbeil-Essonne, FRA., Bell, E., Curry, E. W., Megchelenbrink, W., Jouneau, L., Brochard, V., Tomaz, R. A., Mau, K. H. T., Atlasi, Y., de Souza, R. A., Marks, H., Stunnenberg, H. G., Jouneau, A., Azuara, V., Jouneau, Alice, Azuara, Véronique, and ProdInra, Archive Ouverte
- Subjects
0301 basic medicine ,CHROMATIN ,Transcription, Genetic ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,Stem cells ,Mice ,0302 clinical medicine ,BINDING ,MEDIATOR ,lcsh:Science ,méthylation ,Induced pluripotent stem cell ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Regulation of gene expression ,Multidisciplinary ,Mediator Complex ,Gene Expression Regulation, Developmental ,Mouse Embryonic Stem Cells ,Cell biology ,Chromatin ,Multidisciplinary Sciences ,TRANSCRIPTION FACTORS ,Enhancer Elements, Genetic ,CpG site ,Receptors, Estrogen ,GROUND-STATE ,DNA methylation ,embryonic structures ,Science & Technology - Other Topics ,RNA Polymerase II ,TRANSITION ,Germ Layers ,Protein Binding ,musculoskeletal diseases ,Pluripotent Stem Cells ,Embryonic stem cells ,Science ,education ,chemical and pharmacologic phenomena ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,Developmental biology ,parasitic diseases ,pluripotence ,Animals ,enhancer ,facteur de transcription ,natural sciences ,Enhancer ,Molecular Biology ,Science & Technology ,General Chemistry ,DNA Methylation ,pluripotency ,Embryonic stem cell ,GENE ,030104 developmental biology ,nervous system ,Epiblast ,IDENTITY ,lcsh:Q ,CpG Islands ,EMBRYONIC STEM-CELLS ,030217 neurology & neurosurgery - Abstract
Clusters of enhancers, referred as to super-enhancers (SEs), control the expression of cell identity genes. The organisation of these clusters, and how they are remodelled upon developmental transitions remain poorly understood. Here, we report the existence of two types of enhancer units within SEs typified by distinctive CpG methylation dynamics in embryonic stem cells (ESCs). We find that these units are either prone for decommissioning or remain constitutively active in epiblast stem cells (EpiSCs), as further established in the peri-implantation epiblast in vivo. Mechanistically, we show a pivotal role for ESRRB in regulating the activity of ESC-specific enhancer units and propose that the developmentally regulated silencing of ESRRB triggers the selective inactivation of these units within SEs. Our study provides insights into the molecular events that follow the loss of ESRRB binding, and offers a mechanism by which the naive pluripotency transcriptional programme can be partially reset upon embryo implantation., Clusters of enhancers, called super-enhancers (SEs), control the expression of cell identity genes. Here, the authors identify two types of enhancer units within SEs in ESCs, characterised by distinctive CpG methylation dynamics, and find that ESRRB regulates the enhancer units decommissioned at exit from naive pluripotency.
- Published
- 2020