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

TitleTranscriptional activation by Oct4 is sufficient for the maintenance and induction of pluripotency.
Publication TypeJournal Article
Year of Publication2012
AuthorsHammachi F, Morrison GM, Sharov AA, Livigni A, Narayan S, Papapetrou EP, O'Malley J, Kaji K, Ko MSH, Ptashne M, Brickman JM
JournalCell Rep
Date Published2012 Feb 23
KeywordsAnimals, Cell Differentiation, Cell Line, DNA, Embryonic Stem Cells, Gene Expression Regulation, Developmental, Humans, Induced Pluripotent Stem Cells, Leukemia Inhibitory Factor, Mice, Mutation, Octamer Transcription Factor-3, Protein Binding, Recombinant Fusion Proteins, Repressor Proteins, Transcriptional Activation, Xenopus

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.

Alternate JournalCell Rep
PubMed ID22832160
PubMed Central IDPMC3778438
Grant List079249 / / Wellcome Trust / United Kingdom
BB/C506605 / / Biotechnology and Biological Sciences Research Council / United Kingdom
G0701428 / / Medical Research Council / United Kingdom
G0701429 / / Medical Research Council / United Kingdom
Z01AG AG000656 / AG / NIA NIH HHS / United States
Z01AG000662 / AG / NIA NIH HHS / United States