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

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)11537-11549
Number of pages13
JournalNucleic acids research
Volume49
Issue number20
DOIs
StatePublished - Nov 18 2021

All Science Journal Classification (ASJC) codes

  • Genetics

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