Display options
Cite
Gao R, Helfant LJ, Wu T, et al. A balancing act in transcription regulation by response regulators: titration of transcription factor activity by decoy DNA binding sites. Nucleic Acids Res. 2021;49(20):11537-11549doi: 10.1093/nar/gkab935.
Gao, R., Helfant, L. J., Wu, T., Li, Z., Brokaw, S. E., & Stock, A. M. (2021). A balancing act in transcription regulation by response regulators: titration of transcription factor activity by decoy DNA binding sites. Nucleic acids research, 49(20), 11537-11549. https://doi.org/10.1093/nar/gkab935
Gao, Rong, et al. "A balancing act in transcription regulation by response regulators: titration of transcription factor activity by decoy DNA binding sites." Nucleic acids research vol. 49,20 (2021): 11537-11549. doi: https://doi.org/10.1093/nar/gkab935
Gao R, Helfant LJ, Wu T, Li Z, Brokaw SE, Stock AM. A balancing act in transcription regulation by response regulators: titration of transcription factor activity by decoy DNA binding sites. Nucleic Acids Res. 2021 Nov 18;49(20):11537-11549. doi: 10.1093/nar/gkab935. PMID: 34669947; PMCID: PMC8599769.
Copy Download .nbib Format: NLM
Share it on

Nucleic Acids Res. 2021 Nov 18;49(20):11537-11549. doi: 10.1093/nar/gkab935.

A balancing act in transcription regulation by response regulators: titration of transcription factor activity by decoy DNA binding sites.

Nucleic acids research

Rong Gao, Libby J Helfant, Ti Wu, Zeyue Li, Samantha E Brokaw, Ann M Stock

Affiliations

  1. Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Rutgers University - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

PMID: 34669947 PMCID: PMC8599769 DOI: 10.1093/nar/gkab935

Abstract

Studies of transcription regulation are often focused on binding of transcription factors (TFs) to a small number of promoters of interest. It is often assumed that TFs are in great excess to their binding sites (TFBSs) and competition for TFs between DNA sites is seldom considered. With increasing evidence that TFBSs are exceedingly abundant for many TFs and significant variations in TF and TFBS numbers occur during growth, the interplay between a TF and all TFBSs should not be ignored. Here, we use additional decoy DNA sites to quantitatively analyze how the relative abundance of a TF to its TFBSs impacts the steady-state level and onset time of gene expression for the auto-activated Escherichia coli PhoB response regulator. We show that increasing numbers of decoy sites progressively delayed transcription activation and lowered promoter activities. Perturbation of transcription regulation by additional TFBSs did not require extreme numbers of decoys, suggesting that PhoB is approximately at capacity for its DNA sites. Addition of decoys also converted a graded response to a bi-modal response. We developed a binding competition model that captures the major features of experimental observations, providing a quantitative framework to assess how variations in TFs and TFBSs influence transcriptional responses.

© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

References

  1. Cell. 2018 Mar 22;173(1):196-207.e14 - PubMed
  2. Phys Rev E Stat Nonlin Soft Matter Phys. 2014 Jan;89(1):012702 - PubMed
  3. Nature. 2008 May 8;453(7192):246-50 - PubMed
  4. Cell Chem Biol. 2016 Feb 18;23(2):214-224 - PubMed
  5. Annu Rev Microbiol. 2016 Sep 8;70:103-24 - PubMed
  6. Nat Methods. 2014 May;11(5):508-20 - PubMed
  7. Cell. 2014 Mar 13;156(6):1312-1323 - PubMed
  8. Cell. 2014 Apr 24;157(3):624-35 - PubMed
  9. Mol Syst Biol. 2012 Mar 27;8:576 - PubMed
  10. Nat Biotechnol. 2016 Jan;34(1):104-10 - PubMed
  11. PLoS Genet. 2013 Oct;9(10):e1003927 - PubMed
  12. Genome Res. 2017 Jan;27(1):87-94 - PubMed
  13. Mol Syst Biol. 2012;8:620 - PubMed
  14. mBio. 2015 May 26;6(3):e00686-15 - PubMed
  15. Annu Rev Microbiol. 2011;65:189-213 - PubMed
  16. BMC Biol. 2018 Aug 16;16(1):91 - PubMed
  17. J Bacteriol. 2017 Aug 22;199(18): - PubMed
  18. Genes Dev. 2006 Oct 1;20(19):2754-67 - PubMed
  19. BMC Evol Biol. 2019 Mar 1;19(1):67 - PubMed
  20. Annu Rev Microbiol. 2019 Sep 8;73:507-528 - PubMed
  21. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4138-43 - PubMed
  22. Nat Rev Genet. 2007 Jun;8(6):450-61 - PubMed
  23. mBio. 2017 May 16;8(3): - PubMed
  24. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):691-6 - PubMed
  25. Annu Rev Microbiol. 2008;62:193-210 - PubMed
  26. Nat Genet. 2004 May;36(5):486-91 - PubMed
  27. Trends Microbiol. 2015 Aug;23(8):463-7 - PubMed
  28. Mol Syst Biol. 2009;5:272 - PubMed
  29. Mol Gen Genet. 1998 Feb;257(4):469-77 - PubMed
  30. J Mol Biol. 2006 Jun 16;359(4):1107-24 - PubMed
  31. Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):672-7 - PubMed
  32. PLoS One. 2012;7(10):e47314 - PubMed
  33. Phys Biol. 2010 Aug 23;7(3):036005 - PubMed
  34. Cell Rep. 2018 Sep 11;24(11):3061-3071.e6 - PubMed
  35. PLoS Pathog. 2014 Jun 12;10(6):e1004174 - PubMed
  36. Curr Opin Microbiol. 2010 Apr;13(2):184-9 - PubMed
  37. mSystems. 2020 May 19;5(3): - PubMed
  38. J Bacteriol. 2007 Mar;189(5):1974-82 - PubMed
  39. Antimicrob Agents Chemother. 2015 Apr;59(4):2223-35 - PubMed
  40. Nucleic Acids Res. 2021 Jan 25;49(2):1163-1172 - PubMed
  41. PLoS Comput Biol. 2017 Apr 17;13(4):e1005491 - PubMed
  42. Biochemistry. 2013 Nov 19;52(46):8177-86 - PubMed
  43. Mol Syst Biol. 2010 Dec 21;6:452 - PubMed
  44. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5 - PubMed
  45. PLoS Biol. 2021 Jun 25;19(6):e3001306 - PubMed
  46. Nucleic Acids Res. 2016 Mar 18;44(5):2058-74 - PubMed
  47. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4016-21 - PubMed
  48. Nucleic Acids Res. 2008 Jul;36(12):3950-5 - PubMed
  49. J Bacteriol. 2001 Nov;183(21):6384-93 - PubMed
  50. J Mol Biol. 2010 Aug 27;401(4):671-80 - PubMed
  51. Annu Rev Microbiol. 2019 Sep 8;73:175-197 - PubMed
  52. Mol Syst Biol. 2008;4:161 - PubMed
  53. Nat Commun. 2015 Jan 12;6:5829 - PubMed
  54. Elife. 2020 Aug 18;9: - PubMed
  55. Nat Commun. 2020 Nov 24;11(1):5961 - PubMed
  56. Phys Rev E. 2020 Nov;102(5-1):052410 - PubMed
  57. Transcription. 2016 Aug 7;7(4):115-20 - PubMed
  58. Biophys J. 2010 May 19;98(9):2024-31 - PubMed
  59. Nat Chem Biol. 2019 Feb;15(2):111-114 - PubMed
  60. Nucleic Acids Res. 1990 Aug 11;18(15):4631 - PubMed
  61. Science. 2012 May 18;336(6083):911-5 - PubMed
  62. Nature. 2005 Jul 28;436(7050):588-92 - PubMed
  63. Cell. 2016 Aug 25;166(5):1282-1294.e18 - PubMed
  64. J Bacteriol. 1974 Sep;119(3):736-47 - PubMed
  65. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16659-64 - PubMed

Publication Types

Grant support