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XB-ART-45701
Cell Rep February 23, 2012; 1 (2): 99-109.
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Transcriptional activation by Oct4 is sufficient for the maintenance and induction of pluripotency.

Hammachi F , Morrison GM , Sharov AA , Livigni A , Narayan S , Papapetrou EP , O'Malley J , Kaji K , Ko MS , Ptashne M , Brickman JM .


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.

PubMed ID: 22832160
PMC ID: PMC3778438
Article link: Cell Rep
Grant support: [+]

Species referenced: Xenopus
Genes referenced: bmp4 cdh1 cdx2 fgf4 gsc klf4 lif mixer myc npat pou5f3.1 rexo1 rpl7 sox17a sox2 tbp tra


Article Images: [+] show captions
References [+] :
Ang, Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. 2011, Pubmed