TY - JOUR
T1 - Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency
AU - Bell, Emma
AU - Curry, Edward W.
AU - Megchelenbrink, Wout
AU - Jouneau, Luc
AU - Brochard, Vincent
AU - Tomaz, Rute A.
AU - Mau, King Hang T.
AU - Atlasi, Yaser
AU - de Souza, Roshni A.
AU - Marks, Hendrik
AU - Stunnenberg, Hendrik G.
AU - Jouneau, Alice
AU - Azuara, Véronique
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85081024442&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-14916-7
DO - 10.1038/s41467-020-14916-7
M3 - Article
C2 - 32111830
AN - SCOPUS:85081024442
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1112
ER -