ArticleGenome biology2012
Functional analysis of transcription factor binding sites in human promoters.
Article in Genome biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.
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- Decoding cis-regulatory elements in the germline of the human malaria vector Anopheles gambiae.Communications biology · 2026Article
- YY1 Interacts with Promoter R-Loops to Regulate Transcription.Journal of the American Chemical Society · 2026Article
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- Promoter Motif Profiling and Binding Site Distribution Analysis of Transcription Factors Predict Auto- and Cross-Regulatory Mechanisms inInternational journal of molecular sciences · 2025Article
- Review
- Evolution and Comparative Genomics of the Transforming Growth Factor-β-Related Proteins in Nile Tilapia.Molecular biotechnology · 2025Article
- Benchmarking transcription factor binding site prediction models: a comparative analysis on synthetic and biological data.Briefings in bioinformatics · 2025Article
- CREATE: cell-type-specific cis-regulatory element identification via discrete embedding.Nature communications · 2025Article
- Predicting gene expression changes from chromatin structure modification.NPJ systems biology and applications · 2025Article
- Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.Developmental cell · 2025Article
- Granzyme mRNA-miRNA interaction and its implication to functional impact.Genes & genomics · 2024Article
- Genetic polymorphism in untranslated regions of PRKCZ influences mRNA structure, stability and binding sites.BMC cancer · 2024Article
- Role of Csdc2 in Regulating Secondary Hair Follicle Growth in Cashmere Goats.International journal of molecular sciences · 2024Article
- Assessing next-generation sequencing-based computational methods for predicting transcriptional regulators with query gene sets.Briefings in bioinformatics · 2024Review
- White-opaque switching inMicrobiology and molecular biology reviews : MMBR · 2024Review
- Interpretable prediction of mRNA abundance from promoter sequence using contextual regression models.NAR genomics and bioinformatics · 2024Article
- MAE-seq refines regulatory elements across the genome.Nucleic acids research · 2024Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe binding of transcription factors to specific locations in the genome is integral to the orchestration of transcriptional regulation in cells. To characterize transcription factor binding site function on a large scale, we predicted and mutagenized 455 binding sites in human promoters. We carried out functional tests on these sites in four different immortalized human cell lines using transient transfections with a luciferase reporter assay, primarily for the transcription factors CTCF, GABP, GATA2, E2F, STAT, and YY1.
resultsIn each cell line, between 36% and 49% of binding sites made a functional contribution to the promoter activity; the overall rate for observing function in any of the cell lines was 70%. Transcription factor binding resulted in transcriptional repression in more than a third of functional sites. When compared with predicted binding sites whose function was not experimentally verified, the functional binding sites had higher conservation and were located closer to transcriptional start sites (TSSs). Among functional sites, repressive sites tended to be located further from TSSs than were activating sites. Our data provide significant insight into the functional characteristics of YY1 binding sites, most notably the detection of distinct activating and repressing classes of YY1 binding sites. Repressing sites were located closer to, and often overlapped with, translational start sites and presented a distinctive variation on the canonical YY1 binding motif.
conclusionsThe genomic properties that we found to associate with functional TF binding sites on promoters -- conservation, TSS proximity, motifs and their variations -- point the way to improved accuracy in future TFBS predictions.
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