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

Fella Hammachi, Gillian M. Morrison, Alexei A. Sharov, Alessandra Livigni, Santosh Narayan, Eirini P. Papapetrou, James O'Malley, Keisuke Kaji, Minoru Ko, Mark Ptashne, Joshua M. Brickman

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)99-109
Number of pages11
JournalCell Reports
Volume1
Issue number2
DOIs
Publication statusPublished - 2012 Feb 23
Externally publishedYes

Fingerprint

Stem cells
Transcriptional Activation
Fusion reactions
Chemical activation
Maintenance
Embryonic Stem Cells
Genes
Induced Pluripotent Stem Cells
Xenopus
Cytokines
Phenotype
In Vitro Techniques
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hammachi, F., Morrison, G. M., Sharov, A. A., Livigni, A., Narayan, S., Papapetrou, E. P., ... Brickman, J. M. (2012). Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency. Cell Reports, 1(2), 99-109. https://doi.org/10.1016/j.celrep.2011.12.002

Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency. / Hammachi, Fella; Morrison, Gillian M.; Sharov, Alexei A.; Livigni, Alessandra; Narayan, Santosh; Papapetrou, Eirini P.; O'Malley, James; Kaji, Keisuke; Ko, Minoru; Ptashne, Mark; Brickman, Joshua M.

In: Cell Reports, Vol. 1, No. 2, 23.02.2012, p. 99-109.

Research output: Contribution to journalArticle

Hammachi, F, Morrison, GM, Sharov, AA, Livigni, A, Narayan, S, Papapetrou, EP, O'Malley, J, Kaji, K, Ko, M, Ptashne, M & Brickman, JM 2012, 'Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency', Cell Reports, vol. 1, no. 2, pp. 99-109. https://doi.org/10.1016/j.celrep.2011.12.002
Hammachi F, Morrison GM, Sharov AA, Livigni A, Narayan S, Papapetrou EP et al. Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency. Cell Reports. 2012 Feb 23;1(2):99-109. https://doi.org/10.1016/j.celrep.2011.12.002
Hammachi, Fella ; Morrison, Gillian M. ; Sharov, Alexei A. ; Livigni, Alessandra ; Narayan, Santosh ; Papapetrou, Eirini P. ; O'Malley, James ; Kaji, Keisuke ; Ko, Minoru ; Ptashne, Mark ; Brickman, Joshua M. / Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency. In: Cell Reports. 2012 ; Vol. 1, No. 2. pp. 99-109.
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