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

First Author  Bell E Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  1112
PubMed ID  32111830 Mgi Jnum  J:287124
Mgi Id  MGI:6401661 Doi  10.1038/s41467-020-14916-7
Citation  Bell E, et al. (2020) Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency. Nat Commun 11(1):1112
abstractText  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.
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