Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency
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 functi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471100012X |
| _version_ | 1818808773123244032 |
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| author | Fella Hammachi Gillian M. Morrison Alexei A. Sharov Alessandra Livigni Santosh Narayan Eirini P. Papapetrou James O'Malley Keisuke Kaji Minoru S.H. Ko Mark Ptashne Joshua M. Brickman |
| author_facet | Fella Hammachi Gillian M. Morrison Alexei A. Sharov Alessandra Livigni Santosh Narayan Eirini P. Papapetrou James O'Malley Keisuke Kaji Minoru S.H. Ko Mark Ptashne Joshua M. Brickman |
| author_sort | Fella Hammachi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T19:46:53Z |
| format | Article |
| id | doaj.art-d1bd2d8f5195405882085d6c2bf8d156 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-18T19:46:53Z |
| publishDate | 2012-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-d1bd2d8f5195405882085d6c2bf8d1562022-12-21T20:55:18ZengElsevierCell Reports2211-12472012-02-01129910910.1016/j.celrep.2011.12.002Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of PluripotencyFella Hammachi0Gillian M. Morrison1Alexei A. Sharov2Alessandra Livigni3Santosh Narayan4Eirini P. Papapetrou5James O'Malley6Keisuke Kaji7Minoru S.H. Ko8Mark Ptashne9Joshua M. Brickman10MRC Centre for Regenerative Medicine - Institute for Stem Cell Research, School of Biological Sciences, 5 Little France Drive, University of Edinburgh, EH16 4UU Edinburgh, UKMRC Centre for Regenerative Medicine - Institute for Stem Cell Research, School of Biological Sciences, 5 Little France Drive, University of Edinburgh, EH16 4UU Edinburgh, UKLaboratory of Genetics, National Institute on Aging, NIH Biomedical Research Centre, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USAMRC Centre for Regenerative Medicine - Institute for Stem Cell Research, School of Biological Sciences, 5 Little France Drive, University of Edinburgh, EH16 4UU Edinburgh, UKMolecular Biology Program, Memorial Sloan Kettering Cancer Center, 430E 67th St, New York, NY 10065, USACenter for Cell Engineering, Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USAMRC Centre for Regenerative Medicine - Institute for Stem Cell Research, School of Biological Sciences, 5 Little France Drive, University of Edinburgh, EH16 4UU Edinburgh, UKMRC Centre for Regenerative Medicine - Institute for Stem Cell Research, School of Biological Sciences, 5 Little France Drive, University of Edinburgh, EH16 4UU Edinburgh, UKLaboratory of Genetics, National Institute on Aging, NIH Biomedical Research Centre, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USAMolecular Biology Program, Memorial Sloan Kettering Cancer Center, 430E 67th St, New York, NY 10065, USAMRC Centre for Regenerative Medicine - Institute for Stem Cell Research, School of Biological Sciences, 5 Little France Drive, University of Edinburgh, EH16 4UU Edinburgh, UKOct4 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.http://www.sciencedirect.com/science/article/pii/S221112471100012X |
| spellingShingle | Fella Hammachi Gillian M. Morrison Alexei A. Sharov Alessandra Livigni Santosh Narayan Eirini P. Papapetrou James O'Malley Keisuke Kaji Minoru S.H. Ko Mark Ptashne Joshua M. Brickman Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency Cell Reports |
| title | Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency |
| title_full | Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency |
| title_fullStr | Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency |
| title_full_unstemmed | Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency |
| title_short | Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency |
| title_sort | transcriptional activation by oct4 is sufficient for the maintenance and induction of pluripotency |
| url | http://www.sciencedirect.com/science/article/pii/S221112471100012X |
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