Abstract
POSITIVE control of transcription often involves stimulatory protein-protein interactions between regulatory factors and RNA polymerase1. Critical steps in the activation process itself are seldom ascribed to protein–DNA distortions. Activator-induced DNA bending is typically assigned a role in binding-site recognition2, alterations in DNA loop structures3 or optimal positioning of the activator for interaction with polymerase4. Here we present a transcriptional activation mechanism that does not require a signal-induced DNA bend but rather a receptor-induced untwisting of duplex DNA. The allosterically modulated transcription factor MerR is a represser and an Hg(II)-responsive activator of bacterial mercury-resistance genes5–7.Escherichia coliRNA polymerase binds to the MerR–promoter complex but cannot proceed to a transcriptionally active open complex until Hg(II) binds to MerR (ref. 6). Chemical nuclease studies show that the activator form, but not the represser, induces a unique alteration of the helical structure localized at the centre of the DNA-binding site6. Data presented here indicate that this Hg–MerR-induced DNA distortion corresponds to a local underwinding of the spacer region of the promoter by about 33° relative to the MerR–operator complex. The magnitude and the direction of the Hg–MerR-induced change in twist angle are consistent with a positive control mechanism involving reorientation of conserved, but suboptimally phased, promoter elements and are consistent with a role for torsional stress in formation of an open complex.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ptashne, M. Nature 335, 683–689 (1988).
Steitz, T. A. Q. Rev. Biophys. 23, 205–280 (1990).
Lobell, R. B. & Schleif, R. F. Science 250, 528–532 (1990).
Zinkel, S. S. & Crothers, D. M. J. molec. Biol. 219, 201–215 (1991).
O'Halloran, T. V., Frantz, B., Shin, M. K., Ralston, D. M. & Wright, J. G. Cell 56, 119–129 (1989).
Frantz, B. & O'Halloran, T. V. Biochemistry 29, 4747–4751 (1990).
Brown, N. L. et al. Molec. gen. Genet. 202, 143–151 (1986).
O'Halloran, T. V. & Walsh, C. T. Science 235, 211–214 (1987).
Harley, C. B. & Reynolds, R. P. Nucleic Acids Res. 15, 2343–2361 (1987).
Lund, P. A. & Brown, N. L. Nucleic Acids Res. 17, 5517–5527 (1989).
Parkhill, J. & Brown, N. L. Nucleic Acids Res. 18, 5157–5162 (1990).
Heltzel, A., Lee, I. W., Totis, P. A. & Summers, A. O. Biochemistry 29, 9572–9584 (1990).
Wu, H. M. & Crothers, D. M. Nature 308, 509–513 (1984).
Kim, J., Zwieb, C., Wu, C. & Adhya, S. Gene 85, 15–23 (1989).
Kolb, A. & Buc, H. Nucleic Acids Res. 10, 473–484 (1982).
Gamper, H. B. & Hearst, J. E. Cell 29, 81–90 (1982).
Kim, R. & Kim, S.-H. Cold Spring Harb. Symp. quant Biol. 47, 451–454 (1982).
Kim, R., Modrich, P. & Kim, S.-H. Nucleic Acids Res. 12, 7285–7292 (1984).
Wang, J. C., Jacobsen, J. H. & Saucier, J.-M. Nucleic Acids Res. 4, 1225–1241 (1977).
Depew, R. E. & Wang, J. C. Proc. natn. Acad. Sci. U.S.A. 72, 4275–4279 (1975).
Cozzarelli, N. R., Boles, T. C. & White, J. H. in DNA Topology and its Biological Effects (eds Cozzarelli, N. R. & Wang, J. C.) 139–184 (Cold Spring Harbor Laboratory Press, New York, 1990).
Amouyal, M. & Buc, H. J. molec. Biol. 195, 795–808 (1987).
Travers, A. A. Current Opinions struct. Biol. 1, 114–122 (1991).
Trauera, A. A. & Klug, A. in DNA Topology and its Biological Effects (eds Cozzarelli, N. R. & Wang, J. C.) 57–106 (Cold Spring Harbor Laboratory Press, New York, 1990).
Buc, H. et al. in RNA Polymerase and the Regulation of Transcription (eds Reznikoff, W. S. et al.) 115–125 (Elsevier, New York, 1987).
Boroweic, J. A. & Gralla, J. D. J. molec. Biol. 184, 587–598 (1985).
Ayers, D. G., Auble, D. T. & deHaseth, P. L. J. molec. Biol 207, 749–756 (1989).
Thompson, J. F. & Landy, A. Nucleic Acids Res. 16, 9687–9705 (1988).
Watton, S. P. et al. J. Am. chem. Soc. 112, 2824–2826 (1990).
Helmann, J. D., Ballard, B. T. & Walsh, C. T. Science 247, 946–948 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ansari, A., Chael, M. & O'Halloran, T. Allosteric underwinding of DNA is a critical step in positive control of transcription by Hg-MerR. Nature 355, 87–89 (1992). https://doi.org/10.1038/355087a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/355087a0
This article is cited by
-
CueR activates transcription through a DNA distortion mechanism
Nature Chemical Biology (2021)
-
The bacterial multidrug resistance regulator BmrR distorts promoter DNA to activate transcription
Nature Communications (2020)
-
The conserved actinobacterial transcriptional regulator FtsR controls expression of ftsZ and further target genes and influences growth and cell division in Corynebacterium glutamicum
BMC Microbiology (2019)
-
Bacterial sensors define intracellular free energies for correct enzyme metalation
Nature Chemical Biology (2019)
-
Structural Analysis of the Hg(II)-Regulatory Protein Tn501 MerR from Pseudomonas aeruginosa
Scientific Reports (2016)
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.