TY - JOUR
T1 - Loss of the Otx2-Binding Site in the Nanog Promoter Affects the Integrity of Embryonic Stem Cell Subtypes and Specification of Inner Cell Mass-Derived Epiblast
AU - Acampora, Dario
AU - Omodei, Daniela
AU - Petrosino, Giuseppe
AU - Garofalo, Arcomaria
AU - Savarese, Marco
AU - Nigro, Vincenzo
AU - Di Giovannantonio, Luca Giovanni
AU - Mercadante, Vincenzo
AU - Simeone, Antonio
PY - 2016/6/21
Y1 - 2016/6/21
N2 - Mouse embryonic stem cells (ESCs) and the inner cell mass (ICM)-derived epiblast exhibit naive pluripotency. ESC-derived epiblast stem cells (EpiSCs) and the postimplantation epiblast exhibit primed pluripotency. Although core pluripotency factors are well-characterized, additional regulators, including Otx2, recently have been shown to function during the transition from naive to primed pluripotency. Here we uncover a role for Otx2 in the control of the naive pluripotent state. We analyzed Otx2-binding activity in ESCs and EpiSCs and identified Nanog, Oct4, and Sox2 as direct targets. To unravel the Otx2 transcriptional network, we targeted the strongest Otx2-binding site in the Nanog promoter, finding that this site modulates the size of specific ESC-subtype compartments in cultured cells and promotes Nanog expression in vivo, predisposing ICM differentiation to epiblast. Otx2-mediated Nanog regulation thus contributes to the integrity of the ESC state and cell lineage specification in preimplantation development.
AB - Mouse embryonic stem cells (ESCs) and the inner cell mass (ICM)-derived epiblast exhibit naive pluripotency. ESC-derived epiblast stem cells (EpiSCs) and the postimplantation epiblast exhibit primed pluripotency. Although core pluripotency factors are well-characterized, additional regulators, including Otx2, recently have been shown to function during the transition from naive to primed pluripotency. Here we uncover a role for Otx2 in the control of the naive pluripotent state. We analyzed Otx2-binding activity in ESCs and EpiSCs and identified Nanog, Oct4, and Sox2 as direct targets. To unravel the Otx2 transcriptional network, we targeted the strongest Otx2-binding site in the Nanog promoter, finding that this site modulates the size of specific ESC-subtype compartments in cultured cells and promotes Nanog expression in vivo, predisposing ICM differentiation to epiblast. Otx2-mediated Nanog regulation thus contributes to the integrity of the ESC state and cell lineage specification in preimplantation development.
KW - Embryonic stem cells
KW - Nanog
KW - Otx2
KW - Pluripotency
KW - Preimplantation epiblast
UR - http://www.scopus.com/inward/record.url?scp=84975113580&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84975113580&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2016.05.041
DO - 10.1016/j.celrep.2016.05.041
M3 - Article
AN - SCOPUS:84975113580
VL - 15
SP - 2651
EP - 2664
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 12
ER -