Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency

Emma Bell, Edward W Curry, Wout Megchelenbrink, Luc Jouneau, Vincent Brochard, Rute A Tomaz, King Hang T Mau, Yaser Atlasi, Roshni A de Souza, Hendrik Marks, Hendrik G Stunnenberg, Alice Jouneau, Véronique Azuara

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1112
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 28 Feb 2020
Externally publishedYes

Keywords

  • Animals
  • CpG Islands
  • DNA Methylation
  • Enhancer Elements, Genetic/genetics
  • Gene Expression Regulation, Developmental
  • Germ Layers/cytology
  • Mediator Complex/metabolism
  • Mice
  • Mouse Embryonic Stem Cells/metabolism
  • Pluripotent Stem Cells/metabolism
  • Protein Binding
  • RNA Polymerase II/metabolism
  • Receptors, Estrogen/metabolism
  • Transcription, Genetic

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  • Cite this

    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. (2020). Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency. Nature Communications, 11(1), 1112. https://doi.org/10.1038/s41467-020-14916-7