Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naïve pluripotency
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Supporting information
Author(s)
Type
Journal Article
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.
Date Issued
2020-02-28
Date Acceptance
2020-02-08
Citation
Nature Communications, 2020, 11, pp.1-16
ISSN
2041-1723
Publisher
Nature Research (part of Springer Nature)
Start Page
1
End Page
16
Journal / Book Title
Nature Communications
Volume
11
Copyright Statement
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation,
distribution and reproduction in any medium or format, as long as you give appropriate
credit to the original author(s) and the source, provide a link to the Creative Commons
license, and indicate if changes were made. The images or other third party material in
this article are included in the article’s Creative Commons license, unless indicated
otherwise in a credit line to the material. If material is not included in the article’s
Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the
copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.
distribution and reproduction in any medium or format, as long as you give appropriate
credit to the original author(s) and the source, provide a link to the Creative Commons
license, and indicate if changes were made. The images or other third party material in
this article are included in the article’s Creative Commons license, unless indicated
otherwise in a credit line to the material. If material is not included in the article’s
Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the
copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.
Sponsor
Medical Research Council (MRC)
Genesis Research Trust
Genesis Research Trust
Genesis Research Trust
Genesis Research Trust
Medical Research Council (MRC)
Medical Research Council (MRC)
Genesis Research Trust
Genesis Research Trust
The Portuguese Science & Technology foundation (FCT)
Imperial College London
Identifier
https://www.nature.com/articles/s41467-020-14916-7
Grant Number
MR/K00090X/1
01064 / GEN 90
01064 / GEN 90
01033
01033
MR/K500793/1
MR/K500793/1
01012
01012
SFRH/BD/7024/2010
n/a
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
EMBRYONIC STEM-CELLS
DNA METHYLATION
TRANSCRIPTION FACTORS
GROUND-STATE
GENE
CHROMATIN
TRANSITION
IDENTITY
BINDING
MEDIATOR
Animals
CpG Islands
DNA Methylation
Enhancer Elements, Genetic
Gene Expression Regulation, Developmental
Germ Layers
Mediator Complex
Mice
Mouse Embryonic Stem Cells
Pluripotent Stem Cells
Protein Binding
RNA Polymerase II
Receptors, Estrogen
Transcription, Genetic
Pluripotent Stem Cells
Germ Layers
Animals
Mice
RNA Polymerase II
Receptors, Estrogen
DNA Methylation
Transcription, Genetic
Gene Expression Regulation, Developmental
CpG Islands
Protein Binding
Enhancer Elements, Genetic
Mediator Complex
Mouse Embryonic Stem Cells
Publication Status
Published
Article Number
ARTN 1112
Date Publish Online
2020-02-28