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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Bell E,Curry EW,Megchelenbrink W,Jouneau L,Brochard V,Tomaz RA,Mau KHT,Atlasi Y,de Souza RA,Marks H,Stunnenberg HG,Jouneau A,Azuara V

doi

10.1038/s41467-020-14916-7

subject

Has Abstract

pub_date

2020-02-28 00:00:00

pages

1112

issue

1

issn

2041-1723

pii

10.1038/s41467-020-14916-7

journal_volume

11

pub_type

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