Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

A central role for TFIID in the pluripotent transcription circuitry

Nature volume 495, pages 516–519 (2013)Cite this article

Subjects

Abstract

Embryonic stem (ES) cells are pluripotent and characterized by open chromatin and high transcription levels, achieved through auto-regulatory and feed-forward transcription factor loops1,2. ES-cell identity is maintained by a core of factors including Oct4 (also known as Pou5f1), Sox2, Klf4, c-Myc (OSKM) and Nanog2,3,4, and forced expression of the OSKM factors can reprogram somatic cells into induced pluripotent stem cells (iPSCs) resembling ES cells5,6. These gene-specific factors for RNA-polymerase-II-mediated transcription recruit transcriptional cofactors and chromatin regulators that control access to and activity of the basal transcription machinery on gene promoters7,8. How the basal transcription machinery is involved in setting and maintaining the pluripotent state is unclear. Here we show that knockdown of the transcription factor IID (TFIID) complex affects the pluripotent circuitry in mouse ES cells and inhibits reprogramming of fibroblasts. TFIID subunits and the OSKM factors form a feed-forward loop to induce and maintain a stable transcription state. Notably, transient expression of TFIID subunits greatly enhanced reprogramming. These results show that TFIID is critical for transcription-factor-mediated reprogramming. We anticipate that, by creating plasticity in gene expression programs, transcription complexes such as TFIID assist reprogramming into different cellular states.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: High expression of TFIID is required for maintaining ES cell identity.
Figure 2: TFIID is part of the pluripotency circuitry and is required for reprogramming.
Figure 3: TFIID potentiates reprogramming to pluripotent cells.
Figure 4: TAF contributions to reprogramming and developmental potential of iPSCs.

Similar content being viewed by others

Accession codes

Primary accessions

ArrayExpress

Data deposits

DNA microarray data have been deposited in the public ArrayExpress database under accessions E-TABM-1217 and E-TABM-1218.

References

  1. Efroni, S. et al. Global transcription in pluripotent embryonic stem cells. Cell Stem Cell 2, 437–447 (2008)

    Article  CAS  Google Scholar 

  2. Jaenisch, R. & Young, R. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132, 567–582 (2008)

    Article  CAS  Google Scholar 

  3. Chen, X. et al. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133, 1106–1117 (2008)

    Article  CAS  Google Scholar 

  4. Kim, J., Chu, J., Shen, X., Wang, J. & Orkin, S. H. An extended transcriptional network for pluripotency of embryonic stem cells. Cell 132, 1049–1061 (2008)

    Article  CAS  Google Scholar 

  5. Yamanaka, S. Elite and stochastic models for induced pluripotent stem cell generation. Nature 460, 49–52 (2009)

    Article  CAS  ADS  Google Scholar 

  6. Hanna, J. et al. Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462, 595–601 (2009)

    Article  CAS  ADS  Google Scholar 

  7. Roeder, R. G. Transcriptional regulation and the role of diverse coactivators in animal cells. FEBS Lett. 579, 909–915 (2005)

    Article  CAS  Google Scholar 

  8. Fuda, N. J., Ardehali, M. B. & Lis, J. T. Defining mechanisms that regulate RNA polymerase II transcription in vivo . Nature 461, 186–192 (2009)

    Article  CAS  ADS  Google Scholar 

  9. Goodrich, J. A. & Tjian, R. Unexpected roles for core promoter recognition factors in cell-type-specific transcription and gene regulation. Nature Rev. Genet. 11, 549–558 (2010)

    Article  CAS  Google Scholar 

  10. Müller, F., Zaucker, A. & Tora, L. Developmental regulation of transcription initiation: more than just changing the actors. Curr. Opin. Genet. Dev. 20, 533–540 (2010)

    Article  Google Scholar 

  11. Vermeulen, M. et al. Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 131, 58–69 (2007)

    Article  CAS  Google Scholar 

  12. Juven-Gershon, T. & Kadonaga, J. T. Regulation of gene expression via the core promoter and the basal transcriptional machinery. Dev. Biol. 339, 225–229 (2010)

    Article  CAS  Google Scholar 

  13. Cler, E., Papai, G., Schultz, P. & Davidson, I. Recent advances in understanding the structure and function of general transcription factor TFIID. Cell. Mol. Life Sci. 66, 2123–2134 (2009)

    Article  CAS  Google Scholar 

  14. Vermeulen, M. et al. Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell 142, 967–980 (2010)

    Article  CAS  Google Scholar 

  15. Loh, Y. H. et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nature Genet. 38, 431–440 (2006)

    Article  CAS  Google Scholar 

  16. Szabó, P. E., Hubner, K., Scholer, H. & Mann, J. R. Allele-specific expression of imprinted genes in mouse migratory primordial germ cells. Mech. Dev. 115, 157–160 (2002)

    Article  Google Scholar 

  17. Chia, N. Y. et al. A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. Nature 468, 316–320 (2010)

    Article  CAS  ADS  Google Scholar 

  18. Liu, Z., Scannell, D. R., Eisen, M. B. & Tjian, R. Control of embryonic stem cell lineage commitment by core promoter factor, TAF3. Cell 146, 720–731 (2011)

    Article  CAS  Google Scholar 

  19. Sandelin, A. et al. Mammalian RNA polymerase II core promoters: insights from genome-wide studies. Nature Rev. Genet. 8, 424–436 (2007)

    Article  CAS  Google Scholar 

  20. Gegonne, A. et al. The general transcription factor TAF7 is essential for embryonic development but not essential for the survival or differentiation of mature T cells. Mol. Cell. Biol. 32, 1984–1997 (2012)

    Article  CAS  Google Scholar 

  21. Voss, A. K. et al. Taube nuss is a novel gene essential for the survival of pluripotent cells of early mouse embryos. Development 127, 5449–5461 (2000)

    CAS  PubMed  Google Scholar 

  22. Maston, G. A. et al. Non-canonical TAF complexes regulate active promoters in human embryonic stem cells. eLife 1, e00068 (2012)

    Article  Google Scholar 

  23. Bieniossek, C. et al. The architecture of human general transcription factor TFIID core complex. Nature (2013)

  24. Loh, Y. H., Zhang, W., Chen, X., George, J. & Ng, H. H. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev. 21, 2545–2557 (2007)

    Article  CAS  Google Scholar 

  25. Bilodeau, S., Kagey, M. H., Frampton, G. M., Rahl, P. B. & Young, R. A. SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state. Genes Dev. 23, 2484–2489 (2009)

    Article  CAS  Google Scholar 

  26. Lessard, J. A. & Crabtree, G. R. Chromatin regulatory mechanisms in pluripotency. Annu. Rev. Cell Dev. Biol. 26, 503–532 (2010)

    Article  CAS  Google Scholar 

  27. Singhal, N. et al. Chromatin-remodeling components of the BAF complex facilitate reprogramming. Cell 141, 943–955 (2010)

    Article  CAS  Google Scholar 

  28. Sterneckert, J., Hoing, S. & Scholer, H. R. Oct4 and more: the reprogramming expressway. Stem Cells 30, 15–21 (2011)

    Article  Google Scholar 

  29. Munoz, J. et al. The quantitative proteomes of human-induced pluripotent stem cells and embryonic stem cells. Mol. Syst. Biol. 7, 550 (2011)

    Article  Google Scholar 

Download references

Acknowledgements

This work is funded by the Netherlands Proteomics Centre, Netherlands Organization for Scientific Research (TOP#700.57.302), Deutsche Forschungsgemeinschaft (DFG Priority Program SPP 1356/2) and the European Union (EUTRACC LSHG-CT-2006-037445). We thank M. Groot Koerkamp and D. van Leenen for microarray analysis, M. de Bruijn and O. Kranenburg for advice on lentiviral knockdown experiments, F. Stewart for help with BAC recombineering, I. Davidson and R. Tjian for TAF cDNA constructs, N. Outchkourov for the GFP-tagging vector, B. Roeder, T. Oelgeschläger and G. Kops for antibodies, M. Stehling for help with the FACS analyses, A. Schambach and C. Baum for the lentiviral OSKM vector, M. Sgodda and T. Cantz for human fibroblasts, M. Radstaak for assistance with human iPSC culture and P. de Graaf, N. Jelluma and M. Vermeulen for critical reading of the manuscript.

Author information

Author notes

  1. W. W. M. Pim Pijnappel, Atze J. Bergsma, Erik van der Wal & Dong Wook Han

    Present address: Present addresses: Department of Pediatrics and Department of Clinical Genetics, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands (W.W.M.P.P.; A.J.B.; E.v.d.W.); Department of Stem Cell Biology, School of Medicine, SMART Institute of Advanced Biomedical Science, Konkuk University, 143701 Seoul, Republic of Korea (D.W.H.).,

  2. W. W. M. Pim Pijnappel and Daniel Esch: These authors contributed equally to this work.

Authors and Affiliations

  1. Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands ,

    W. W. M. Pim Pijnappel, Marijke P. A. Baltissen, Atze J. Bergsma, Phillip Lijnzaad, Katrin Sameith, Frank C. P. Holstege & H. T. Marc Timmers

  2. Netherlands Proteomics Center, 3584 CH Utrecht, The Netherlands ,

    W. W. M. Pim Pijnappel, Marijke P. A. Baltissen, Nikolai Mischerikow, A. F. Maarten Altelaar, Albert J. R. Heck & H. T. Marc Timmers

  3. Department of Pediatrics and Department of Clinical Genetics, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands,

    W. W. M. Pim Pijnappel & Erik van der Wal

  4. Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany ,

    Daniel Esch, Guangming Wu, Erik van der Wal, Dong Wook Han, Hermann vom Bruch, Sören Moritz, Holm Zaehres & Hans R. Schöler

  5. Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, The Netherlands ,

    Nikolai Mischerikow, A. F. Maarten Altelaar & Albert J. R. Heck

Authors
  1. W. W. M. Pim Pijnappel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Esch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marijke P. A. Baltissen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guangming Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nikolai Mischerikow
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Atze J. Bergsma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Erik van der Wal
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dong Wook Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hermann vom Bruch
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sören Moritz
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Phillip Lijnzaad
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A. F. Maarten Altelaar
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Katrin Sameith
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Holm Zaehres
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Albert J. R. Heck
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Frank C. P. Holstege
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Hans R. Schöler
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. H. T. Marc Timmers
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

W.W.M.P.P. and H.T.M.T. initiated the project. W.W.M.P.P., D.E., H.Z., A.J.R.H., F.C.P.H., H.R.S. and H.T.M.T. designed the experiments. M.P.A.B. and W.W.M.P.P. performed lentiviral knockdown and mRNA analysis. N.M., A.F.M.A., W.W.M.P.P. and A.J.R.H. performed and analysed the mass spectrometry experiments. W.W.M.P.P. and F.C.P.H. performed and supervised the mRNA profiling experiments. A.J.B. and W.W.M.P.P. performed the ChIP and enhancer analysis. W.W.M.P.P., D.E., E.v.d.W., D.W.H., H.v.B., S.M., H.Z. and H.T.M.T. performed the reprogramming experiments. P.L. and K.S. contributed to the statistical analysis. G.W. performed the animal experiments. W.W.M.P.P. and H.T.M.T. wrote the manuscript. All authors approved the manuscript.

Corresponding author

Correspondence to H. T. Marc Timmers.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, Supplementary Figures 1-33, Supplementary Tables 1-3 and Supplementary References. (PDF 11537 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pijnappel, W., Esch, D., Baltissen, M. et al. A central role for TFIID in the pluripotent transcription circuitry. Nature 495, 516–519 (2013). https://doi.org/10.1038/nature11970

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature11970

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing
  NODES
INTERN 1
Note 1
Project 1
twitter 1