ArticlePLoS computational biology2010
A quantitative model of transcriptional regulation reveals the influence of binding location on expression.
Article in PLoS computational biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 2 citations in OpenAlex.
- Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT) genomic binding patterns discerns cell-specific cis-regulatory modules.BMC genomics · 2013Pooled it
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- Arid1a regulates cell cycle exit of transit-amplifying cells by inhibiting the Aurka-Cdk1 axis in mouse incisor.Development (Cambridge, England) · 2021Article
- Lessons from eRNAs: understanding transcriptional regulation through the lens of nascent RNAs.Transcription · 2020Review
- Estrogen Receptor, Inflammatory, and FOXO Transcription Factors Regulate Expression of Myasthenia Gravis-Associated Circulating microRNAs.Frontiers in immunology · 2020Article
- Early epigenomic and transcriptional changes reveal Elk-1 transcription factor as a therapeutic target in Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Modelling the gene expression and the DNA-binding in the 3T3-L1 differentiating adipocytes.Adipocyte · 2019Article
- Genome-Wide Identification of Direct RTA Targets Reveals Key Host Factors for Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation.Journal of virology · 2019Article
- Impaired DNA demethylation of C/EBP sites causes premature aging.Genes & development · 2018Article
- Regulation of circadian clock transcriptional output by CLOCK:BMAL1.PLoS genetics · 2018Article
- Associating transcription factors and conserved RNA structures with gene regulation in the human brain.Scientific reports · 2017Article
- Baf60b-mediated ATM-p53 activation blocks cell identity conversion by sensing chromatin opening.Cell research · 2017Article
- Transcriptional regulatory logic of the diurnal cycle in the mouse liver.PLoS biology · 2017Article
- Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis.Scientific reports · 2017Article
- Simvastatin-induced sphingosine 1-phosphate receptor 1 expression is KLF2-dependent in human lung endothelial cells.Pulmonary circulation · 2017Article
- Navigating the Functional Landscape of Transcription Factors via Non-Negative Tensor Factorization Analysis of MEDLINE Abstracts.Frontiers in bioengineering and biotechnology · 2017Article
- Article
- Cancer somatic mutations cluster in a subset of regulatory sites predicted from the ENCODE data.Molecular cancer · 2016Article
- REST regulation of gene networks in adult neural stem cells.Nature communications · 2016Article
- iTAR: a web server for identifying target genes of transcription factors using ChIP-seq or ChIP-chip data.BMC genomics · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Understanding the mechanistic basis of transcriptional regulation has been a central focus of molecular biology since its inception. New high-throughput chromatin immunoprecipitation experiments have revealed that most regulatory proteins bind thousands of sites in mammalian genomes. However, the functional significance of these binding sites remains unclear. We present a quantitative model of transcriptional regulation that suggests the contribution of each binding site to tissue-specific gene expression depends strongly on its position relative to the transcription start site. For three cell types, we show that, by considering binding position, it is possible to predict relative expression levels between cell types with an accuracy approaching the level of agreement between different experimental platforms. Our model suggests that, for the transcription factors profiled in these cell types, a regulatory site's influence on expression falls off almost linearly with distance from the transcription start site in a 10 kilobase range. Binding to both evolutionarily conserved and non-conserved sequences contributes significantly to transcriptional regulation. Our approach also reveals the quantitative, tissue-specific role of individual proteins in activating or repressing transcription. These results suggest that regulator binding position plays a previously unappreciated role in influencing expression and blurs the classical distinction between proximal promoter and distal binding events.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.