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 - Funding Information:
We would like to thank Hitoshi Niwa and Austin Smith for provision of materials; Laxmi M.S. Tirunagari for technical assistance; Michel Sadelain for advice; and Alfonso Martinez Arias, Sally Lowell, Val Wilson, and the entire Brickman and Ptashne labs for critical reading of this manuscript. This work was supported by the BBSRC (BB/C506605), Scottish Funding Council, the Medical Research Council (MRC G0701428) (to J.M.B.), the Intramural Research Program of the NIH, the National Institute on Aging (Z01AG AG000656, Z01AG000662) (to M.S.H.K.), and the New York Stem Cell Science (NYSTEM) Program (C026407) (to M.P.). F.H. was supported by a scholarship from the Algerian Government. J.M.B. is an MRC Senior Non-Clinical Research Fellow.
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.
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U2 - 10.1016/j.celrep.2011.12.002
DO - 10.1016/j.celrep.2011.12.002
M3 - Article
C2 - 22832160
AN - SCOPUS:84861176731
SN - 2211-1247
VL - 1
SP - 99
EP - 109
JO - Cell Reports
JF - Cell Reports
IS - 2
ER -