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Cited by 142Genomics and Chromatin DynamicsGene Regulatory Network AnalysisFungal and yeast genetics research

A quantitative model of transcription factor–activated gene expression

Open access
Kim, Harold D, O'Shea, Erin K·2008·Nature Structural & Molecular Biology
DOI 10.1038/nsmb.1500PMC PMC2696132
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Abstract

A challenge facing biology is to develop quantitative, predictive models of gene regulation. Eukaryotic promoters contain transcription factor binding sites of differing affinity and accessibility, but we understand little about how these variables combine to generate a fine-tuned, quantitative transcriptional response. Here we used the PHO5 promoter in budding yeast to quantify the relationship between transcription factor input and gene expression output, termed the gene-regulation function (GRF). A model that captures variable interactions between transcription factors, nucleosomes and the promoter faithfully reproduced the observed quantitative changes in the GRF that occur upon altering the affinity of transcription factor binding sites, and implicates nucleosome-modulated accessibility of transcription factor binding sites in increasing the diversity of gene expression profiles. This work establishes a quantitative framework that can be applied to predict GRFs of other eukaryotic genes.

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  • VP48 is known to directly interact with chromatin-remodeling cofactors.

    “Because VP48 is known to directly interact with chromatin-remodeling cofactors21–23”

    From Single-molecule states link transcription factor binding to gene expression (2024) · cites this paper as [22]

    The Discussion describes Pho4 binding and chromatin-remodeling kinetics at the PHO5 promoter, but does not address VP48 or direct interactions with remodeling cofactors. Searches for “VP48” and direct physical interactions found no passage supporting the attributed claim. (LLM, conf=0.76)

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Research works printed but not linked: 35

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Cited by

Sorted by citations

Authors
Kim, H. D., & O'Shea, E. K.
Affiliations
Howard Hughes Medical Institute (US)
ORCID
Kim, Harold D
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2008-10-12
Volume
15
Issue
11
Pages
1192-1198
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
DOI
10.1038/nsmb.1500
PMC
PMC2696132
OpenAlex
W2061851611
Cited by
142
References
2
Citations by year
2026: 2 · 2025: 2 · 2024: 6 · 2023: 2 · 2022: 4 · 2021: 8 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 3 · 2016: 7 · 2015: 5 · 2014: 13 · 2013: 18 · 2012: 13
FWCI
5.49
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • University of California, San Francisco
  • National Institute of General Medical Sciences (GM51377, R01GM051377)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
transcription factor binding affinity, nucleosome accessibility, PHO5 promoter, Saccharomyces cerevisiae, eukaryotic gene regulation, promoter architecture, transcriptional response, gene expression variation
MeSH terms
Acid Phosphatase, DNA-Binding Proteins, Models, Genetic, Nucleosomes, Promoter Regions, Genetic, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Fungal, Gene Expression Profiling, Saccharomyces cerevisiae Proteins

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