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

   

Authors:	Hammachi, F.; Morrison, G. M.; Sharov, A. A.; Livigni, A.; Narayan, S.; Papapetrou, E. P.; O'Malley, J.; Kaji, K.; Ko, M. S. H.; Ptashne, M.; Brickman, J. M.
Article Title:	Transcriptional activation by Oct4 is sufficient for the maintenance and induction of pluripotency
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. © 2012 The Authors.
Keywords:	signal transduction; controlled study; gene sequence; human cell; promoter region; mutation; nonhuman; animal cell; mouse; animals; mice; gene targeting; gene overexpression; embryo; embryonic stem cell; transcription initiation; cell line; protein binding; cell renewal; in vivo study; cell differentiation; in vitro study; gene expression regulation; gene expression regulation, developmental; gene activation; dna; hybrid protein; recombinant fusion proteins; messenger rna; molecular recognition; gene repression; embryonic stem cells; cytokine production; dna sequence; pluripotent stem cell; concentration (parameters); repressor proteins; transcriptional activation; genetic code; phenotypic variation; octamer transcription factor 4; octamer transcription factor-3; induced pluripotent stem cells; xenopus; xenopus laevis; leukemia inhibitory factor; regulator gene; oct4 gene
Journal Title:	Cell Reports
Volume:	1
Issue:	2
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2012-02-23
Start Page:	99
End Page:	109
Language:	English
DOI:	10.1016/j.celrep.2011.12.002
PROVIDER:	scopus
PUBMED:	22832160
PMCID:	PMC3778438
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84861176731&partnerID=40&md5=85e0094e1c93677a047b3b514c12e654
Notes:	--- - "Export Date: 4 June 2012" - "Source: Scopus"

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