Exploring the mono-/bistability range of positively autoregulated signaling systems in the presence of competing transcription factor binding sites Article Swipe
Rong Gao
,
Samantha E. Brokaw
,
Zeyue Li
,
Libby J. Helfant
,
Ti Wu
,
Muhammad Imran Malik
,
Ann Stock
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pcbi.1010738
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pcbi.1010738
Binding of transcription factor (TF) proteins to regulatory DNA sites is key to accurate control of gene expression in response to environmental stimuli. Theoretical modeling of transcription regulation is often focused on a limited set of genes of interest, while binding of the TF to other genomic sites is seldom considered. The total number of TF binding sites (TFBSs) affects the availability of TF protein molecules and sequestration of a TF by TFBSs can promote bistability. For many signaling systems where a graded response is desirable for continuous control over the input range, biochemical parameters of the regulatory proteins need be tuned to avoid bistability. Here we analyze the mono-/bistable parameter range for positively autoregulated two-component systems (TCSs) in the presence of different numbers of competing TFBSs. TCS signaling, one of the major bacterial signaling strategies, couples signal perception with output responses via protein phosphorylation. For bistability, competition for TF proteins by TFBSs lowers the requirement for high fold change of the autoregulated transcription but demands high phosphorylation activities of TCS proteins. We show that bistability can be avoided with a low phosphorylation capacity of TCSs, a high TF affinity for the autoregulated promoter or a low fold change in signaling protein levels upon induction. These may represent general design rules for TCSs to ensure uniform graded responses. Examining the mono-/bistability parameter range allows qualitative prediction of steady-state responses, which are experimentally validated in the E . coli CusRS system.
Related Topics
Concepts
Transcription factor
Bistability
Phosphorylation
Biology
Gene
Cell biology
DNA binding site
Signal transduction
Binding site
DNA-binding protein
Regulation of gene expression
Gene expression
Chemistry
Computational biology
Genetics
Promoter
Materials science
Optoelectronics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pcbi.1010738
- OA Status
- gold
- Cited By
- 1
- References
- 71
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4309600436
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4309600436Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1371/journal.pcbi.1010738Digital Object Identifier
- Title
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Exploring the mono-/bistability range of positively autoregulated signaling systems in the presence of competing transcription factor binding sitesWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-11-22Full publication date if available
- Authors
-
Rong Gao, Samantha E. Brokaw, Zeyue Li, Libby J. Helfant, Ti Wu, Muhammad Imran Malik, Ann StockList of authors in order
- Landing page
-
https://doi.org/10.1371/journal.pcbi.1010738Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1371/journal.pcbi.1010738Direct OA link when available
- Concepts
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Transcription factor, Bistability, Phosphorylation, Biology, Gene, Cell biology, DNA binding site, Signal transduction, Binding site, DNA-binding protein, Regulation of gene expression, Gene expression, Chemistry, Computational biology, Genetics, Promoter, Materials science, OptoelectronicsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
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2023: 1Per-year citation counts (last 5 years)
- References (count)
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71Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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