Transcriptional Activation by Oct4 is Sufficient for the Maintenance and Induction of Pluripotency

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2012 Jul 27

PMID 22832160

Citations 37

Authors

Fella Hammachi

Gillian M Morrison

Alexei A Sharov

Alessandra Livigni

Santosh Narayan

Eirini P Papapetrou

James OMalley

Keisuke Kaji

Minoru S H Ko

Mark Ptashne

Joshua M Brickman

Affiliations

Soon will be listed here.

Abstract

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.

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