ArticleNature communications2019
Functional genetic variants can mediate their regulatory effects through alteration of transcription factor binding.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- A 20 Bp Indel ofAnimals : an open access journal from MDPI · 2026Article
- Mapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learning.Nature communications · 2026Article
- Expanded chromatin accessibility mapping explains genetic variation associated with complex traits in liver.American journal of human genetics · 2026Article
- Why 11β-HSD1 inhibitors show variable efficacy in Alzheimer's therapy: an APOE4-dependent HSD11B1 mechanism.Theranostics · 2026Article
- Mutations Upstream of ppp2ca Affect Body Weight in Asian Seabass.Marine biotechnology (New York, N.Y.) · 2025Article
- Expanded Chromatin Accessibility Mapping Explains Genetic Variation Associated with Complex Traits in Liver.medRxiv : the preprint server for health sciences · 2025Article
- Genotype inference from aggregated chromatin accessibility data reveals genetic regulatory mechanisms.Genome biology · 2025Article
- reg-eQTL: Integrating transcription factor effects to unveil regulatory variants.American journal of human genetics · 2025Article
- Epigenetic Impacts of Non-Coding Mutations Deciphered Through Pre-Trained DNA Language Model at Single-Cell Resolution.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Multiomics uncovers the epigenomic and transcriptomic response to viral and bacterial stimulation in turbot.GigaScience · 2025Article
- Interactive effects between lead-cadmium co-exposure and VEGFA gene polymorphisms on renal dysfunction: a gene-environment interaction study.Frontiers in public health · 2025Article
- The transcriptional and cellular landscape of cognitive resilience to Alzheimer's disease.Frontiers in molecular neuroscience · 2025Review
- Article
- Genotype inference from aggregated chromatin accessibility data reveals genetic regulatory mechanisms.bioRxiv : the preprint server for biology · 2024Article
- DNA-binding factor footprints and enhancer RNAs identify functional non-coding genetic variants.Genome biology · 2024Article
- Complex regulatory networks influence pluripotent cell state transitions in human iPSCs.Nature communications · 2024Article
- Parkinson's disease risk enhancers in microglia.iScience · 2024Article
- Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.Human genomics · 2024Article
- Characterizing genetic variation in the regulation of the ER stress response through computational and cis-eQTL analyses.G3 (Bethesda, Md.) · 2023Article
- Using epigenomics to understand cellular responses to environmental influences in diseases.PLoS genetics · 2023Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Functional variants in the genome are usually identified by their association with local gene expression, DNA methylation or chromatin states. DNA sequence motif analysis and chromatin immunoprecipitation studies have provided indirect support for the hypothesis that functional variants alter transcription factor binding to exert their effects. In this study, we provide direct evidence that functional variants can alter transcription factor binding. We identify a multifunctional variant within the TBC1D4 gene encoding a canonical NFκB binding site, and edited it using CRISPR-Cas9 to remove this site. We show that this editing reduces TBC1D4 expression, local chromatin accessibility and binding of the p65 component of NFκB. We then used CRISPR without genomic editing to guide p65 back to the edited locus, demonstrating that this re-targeting, occurring ~182 kb from the gene promoter, is enough to restore the function of the locus, supporting the central role of transcription factors mediating the effects of functional variants.
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