Transcriptional activation by Oct4 is sufficient for the maintenance and induction of pluripotency

TY - JOUR

T1 - Transcriptional activation by Oct4 is sufficient for the maintenance and induction of pluripotency

AU - Hammachi, Fella

AU - Morrison, Gillian M

AU - Sharov, Alexei A

AU - Livigni, Alessandra

AU - Narayan, Santosh

AU - Papapetrou, Eirini P

AU - O'Malley, James

AU - Kaji, Keisuke

AU - Ko, Minoru S H

AU - Ptashne, Mark

AU - Brickman, Joshua M

N1 - Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2012/2/23

Y1 - 2012/2/23

N2 - Oct4 is an essential regulator of pluripotency in vivo and in vitro in embryonic stem cells, as well as a key mediator of the reprogramming of somatic cells into induced pluripotent stem cells. It is not known whether activation and/or repression of specific genes by Oct4 is relevant to these functions. Here, we show that fusion proteins containing the coding sequence of Oct4 or Xlpou91 (the Xenopus homolog of Oct4) fused to activating regions, but not those fused to repressing regions, behave as Oct4, suppressing differentiation and promoting maintenance of undifferentiated phenotypes in vivo and in vitro. An Oct4 activation domain fusion supported embryonic stem cell self-renewal in vitro at lower concentrations than that required for Oct4 while alleviating the ordinary requirement for the cytokine LIF. At still lower levels of the fusion, LIF dependence was restored. We conclude that the necessary and sufficient function of Oct4 in promoting pluripotency is to activate specific target genes.

AB - Oct4 is an essential regulator of pluripotency in vivo and in vitro in embryonic stem cells, as well as a key mediator of the reprogramming of somatic cells into induced pluripotent stem cells. It is not known whether activation and/or repression of specific genes by Oct4 is relevant to these functions. Here, we show that fusion proteins containing the coding sequence of Oct4 or Xlpou91 (the Xenopus homolog of Oct4) fused to activating regions, but not those fused to repressing regions, behave as Oct4, suppressing differentiation and promoting maintenance of undifferentiated phenotypes in vivo and in vitro. An Oct4 activation domain fusion supported embryonic stem cell self-renewal in vitro at lower concentrations than that required for Oct4 while alleviating the ordinary requirement for the cytokine LIF. At still lower levels of the fusion, LIF dependence was restored. We conclude that the necessary and sufficient function of Oct4 in promoting pluripotency is to activate specific target genes.

U2 - 10.1016/j.celrep.2011.12.002

DO - 10.1016/j.celrep.2011.12.002

M3 - Journal article

C2 - 22832160

SN - 2041-5346

VL - 1

SP - 99

EP - 109

JO - Cell Biology International Reports

JF - Cell Biology International Reports

IS - 2

ER -