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Nucleic acids research
11 18, 2021;49 (20): 11537-11549.

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

Rong Gao, Libby J Helfant, Ti Wu, Zeyue Li, Samantha E Brokaw, Ann M Stock
Author Information
  1. Rong Gao: Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Rutgers University - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
  2. Libby J Helfant: Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Rutgers University - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
  3. Ti Wu: Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Rutgers University - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
  4. Zeyue Li: Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Rutgers University - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
  5. Samantha E Brokaw: Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Rutgers University - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
  6. Ann M Stock: Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Molecular Biology, Rutgers University - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. ORCID
PMID: 34669947 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.

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Grants

  1. R35 GM131727/NIGMS NIH HHS

MeSH Term

Binding Sites
DNA
Escherichia coli
Escherichia coli Proteins
Gene Expression Regulation, Bacterial
Nucleotide Motifs
Protein Binding
Transcription Factors

Chemicals

Escherichia coli Proteins
Transcription Factors
DNA
Journal Article Research Support, N.I.H., Extramural
Article has an altmetric score of 6

Word Cloud

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