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 Communjournal_title
Nature communicationsauthors
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 Vdoi
10.1038/s41467-020-14916-7subject
Has Abstractpub_date
2020-02-28 00:00:00pages
1112issue
1issn
2041-1723pii
10.1038/s41467-020-14916-7journal_volume
11pub_type
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