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:

Selectivity of chromatin-remodelling cofactors for ligand-activated transcription

Abstract

An array of regulatory protein and multi-subunit cofactors has been identified1 that directs eukaryotic gene transcription. However, establishing the specific functions of various related cofactors has been difficult owing to the limitations inherent in assaying transcription in animals and cells indirectly. Here we describe, using an integrated chromatin-dependent reconstituted transcription reaction, the purification and identification of a multi-subunit cofactor (PBAF)2 that is necessary for ligand-dependent transactivation by nuclear hormone receptors. A highly related cofactor, human SWI/SNF3, and the ISWI-containing chromatin-remodelling complex ACF4 both fail to potentiate transcription. We also show that transcriptional activation mediated by nuclear hormone receptors requires TATA-binding protein (TBP)-associated factors (TAFs) as well as the multi-subunit cofactors ARC5/CRSP6. These studies demonstrate functional selectivity amongst highly related complexes involved in gene regulation and help define a more complete set of factors and cofactors required to activate transcription.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Purification of a cofactor required for activated transcription on chromatin templates in vitro.
Figure 2: Chromatin-dependent transcription cofactor defined as PBAF.
Figure 3: Purification of other chromatin-remodelling complexes.
Figure 4: Specific requirement for PBAF chromatin cofactor by human enhancer binding factors.
Figure 5: BAF, TAF, and ARC requirement for ligand-dependent activated transcription.

Similar content being viewed by others

References

  1. Lemon, B. & Tjian, R. Orchestrated response: a symphony of transcription factors for gene control. Genes Dev. 14, 2551–2569 (2000).

    Article  CAS  Google Scholar 

  2. Xue, Y. T. et al. The human SWI/SNF-B chromatin-remodeling complex is related to yeast Rsc and localizes at kinetochores of mitotic chromosomes. Proc. Natl Acad. Sci. USA 97, 13015–13020 (2000).

    Article  ADS  CAS  Google Scholar 

  3. Kwon, H., Imbalzano, A. N., Khavari, P. A., Kingston, R. E. & Green, M. R. Nucleosome disruption and enhancement of activator binding by a human SWI/SNF complex. Nature 370, 477–481 (1994).

    Article  ADS  CAS  Google Scholar 

  4. Ito, T. et al. ACF consists of two subunits, Acf1 and ISWI, that function cooperatively in the ATP-dependent catalysis of chromatin assembly. Genes Dev. 13, 1529–1539 (1999).

    Article  CAS  Google Scholar 

  5. Näär, A. M. et al. Composite coactivator ARC mediates chromatin-directed transcriptional activation. Nature 398, 828–832 (1999).

    Article  ADS  Google Scholar 

  6. Ryu, S., Zhou, S., Ladurner, A. G. & Tjian, R. The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1. Nature 397, 446–450 (1999).

    Article  ADS  CAS  Google Scholar 

  7. Kingston, R. E. & Narlikar, G. J. ATP-dependent remodeling and acetylation as regulators of chromatin fluidity. Genes Dev. 13, 2339–2352 (1999).

    Article  CAS  Google Scholar 

  8. Rachez, C. et al. Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 398, 824–828 (1999).

    Article  ADS  CAS  Google Scholar 

  9. Kwok, R. P. et al. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 370, 223–226 (1994).

    Article  ADS  CAS  Google Scholar 

  10. Ge, H. & Roeder, R. G. Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes. Cell 78, 513–523 (1994).

    Article  CAS  Google Scholar 

  11. Merino, A., Madden, K. R., Lane, W. S., Champoux, J. J. & Reinberg, D. DNA topoisomerase I is involved in both repression and activation of transcription. Nature 365, 227–232 (1993).

    Article  ADS  CAS  Google Scholar 

  12. Wang, W. et al. Diversity and specialization of mammalian SWI/SNF complexes. Genes Dev. 10, 2117–2130 (1996).

    Article  CAS  Google Scholar 

  13. Khavari, P. A., Peterson, C. L., Tamkun, J. W., Mendel, D. B. & Crabtree, G. R. BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature 366, 170–174 (1993).

    Article  ADS  CAS  Google Scholar 

  14. Muchardt, C. & Yaniv, M. A human homologue of Saccharomyces cerevisiae SNF2/SWI2 and Drosophila brm genes potentiates transcriptional activation by the glucocorticoid receptor. EMBO J. 12, 4279–4290 (1993).

    Article  CAS  Google Scholar 

  15. Reyes, J. C., Muchardt, C. & Yaniv, M. Components of the human SWI/SNF complex are enriched in active chromatin and are associated with the nuclear matrix. J. Cell Biol. 137, 263–274 (1997).

    Article  CAS  Google Scholar 

  16. Jacobson, R. H., Ladurner, A. G., King, D. S. & Tjian, R. Structure and function of a human TAFII250 double bromodomain module. Science 288, 1422–1425 (2000).

    Article  ADS  CAS  Google Scholar 

  17. Nie, Z. et al. A specificity and targeting subunit of a human SWI/SNF family-related chromatin-remodeling complex. Mol. Cell. Biol. 20, 8879–8888 (2000).

    Article  CAS  Google Scholar 

  18. Tsukiyama, T., Daniel, C., Tamkun, J. & Wu, C. ISWI, a member of the SWI2/SNF2 ATPase family, encodes the 140 kDa subunit of the nucleosome remodeling factor. Cell 83, 1021–1026 (1995).

    Article  CAS  Google Scholar 

  19. LeRoy, G., Orphanides, G., Lane, W. S. & Reinberg, D. Requirement of RSF and FACT for transcription of chromatin templates in vitro. Science 282, 1900–1904 (1998).

    Article  ADS  CAS  Google Scholar 

  20. Näär, A. M. et al. Chromatin, TAFs, and a novel multiprotein coactivator are required for synergistic activation by Sp1 and SREBP-1a in vitro. Genes Dev. 12, 3020–3031 (1998).

    Article  Google Scholar 

  21. Fondell, J. D., Guermah, M., Malik, S. & Roeder, R. G. Thyroid hormone receptor-associated proteins and general positive cofactors mediate thyroid hormone receptor function in the absence of the TATA box-binding protein-associated factors of TFIID. Proc. Natl Acad. Sci. USA 96, 1959–1964 (1999).

    Article  ADS  CAS  Google Scholar 

  22. Gu, W. et al. A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. Mol. Cell 3, 97–108 (1999).

    Article  CAS  Google Scholar 

  23. Lee, T. I. et al. Redundant roles for the TFIID and SAGA complexes in global transcription. Nature 405, 701–704 (2000).

    Article  ADS  CAS  Google Scholar 

  24. Fryer, C. J. & Archer, T. K. Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex. Nature 393, 88–91 (1998).

    Article  ADS  CAS  Google Scholar 

  25. Krebs, J. E., Kuo, M. H., Allis, C. D. & Peterson, C. L. Cell cycle-regulated histone acetylation required for expression of the yeast HO gene. Genes Dev. 13, 1412–1421 (1999).

    Article  CAS  Google Scholar 

  26. Armstrong, J. A., Bieker, J. J. & Emerson, B. M. A SWI/SNF-related chromatin remodeling complex, E-RC1, is required for tissue-specific transcriptional regulation by EKLF in vitro. Cell 95, 93–104 (1998).

    Article  CAS  Google Scholar 

  27. Kraus, W. L. & Kadonaga, J. T. p300 and estrogen receptor cooperatively activate transcription via differential enhancement of initiation and reinitiation. Genes Dev. 12, 331–342 (1998).

    Article  CAS  Google Scholar 

  28. Kal, A. J., Mahmoudi, T., Zak, N. B. & Verrijzer, C. P. The Drosophila brahma complex is an essential coactivator for the trithorax group protein zeste. Genes Dev. 14, 1058–1071 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Sif, S., Saurin, A. J., Imbalzano, A. N. & Kingston, R. E. Purification and characterization of mSin3A-containing Brg1 and hBrm chromatin remodeling complexes. Genes Dev. 15, 603–618 (2001).

    Article  CAS  Google Scholar 

  30. Bultman, S. et al. A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Mol. Cell 6, 1287–1295 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank R. Bell and M. Haggart for technical assistance; W. Wang for providing affinity-purified antibodies raised against BAF180; G. Crabtree for antibodies raised against BRG1 and multiple BAFs; N. Tanese for antibodies raised against BAF250; R. Kingston and A. Imbalzano for antibodies raised against BRM; D. Fyodorov and J. Kadonaga for providing recombinant viruses for expression of ACF and for purified rACF used in initial experiments; S. Ryu for purified TFIIH, rPC4, rTopo I, and rTBP, as well as the G3B-CAT plasmid; A. Näär for purified rSREBP-1a as well as LDLR-CAT and GST-activation domain expression plasmids; J.-L. Chen for the PPARγ cDNA and ligand; L. Freedman, R. Freiman, J. Kadonaga, P. Kaufman, M. Marr, D. Taatjes, and W. Wang for comments on the manuscript, and all members of our laboratory for helpful discussions and technical advice. B.L. was recipient of a National Research Service Award during most of this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert Tjian.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lemon, B., Inouye, C., King, D. et al. Selectivity of chromatin-remodelling cofactors for ligand-activated transcription. Nature 414, 924–928 (2001). https://doi.org/10.1038/414924a

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/414924a

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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