ArticleProceedings of the National Academy of Sciences of the United States of America2017
Systematic dissection of genomic features determining transcription factor binding and enhancer function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
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Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 187 citations in OpenAlex.
- Meta-analysis of massively parallel reporter assays enables prediction of regulatory function across cell types.Human mutation · 2019Pooled it
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- Dynamic neuro-immune regulation of psychiatric risk loci in human neurons.Nature communications · 2026Article
- Promoter identity shapes splicing outcomes and fidelity.Nature communications · 2026Article
- Combinatorial transcription factor interactions drive modular gene regulatory networks.bioRxiv : the preprint server for biology · 2026Article
- Elastic enhancer network tunes equilibrium thermodynamics of liquid liquid phase separation in super enhancers.iScience · 2026Article
- PoolParty: streamlined design of DNA sequence libraries in Python.bioRxiv : the preprint server for biology · 2026Article
- Article
- Motif-based models accurately predict cell type-specific distal regulatory elements.Nature communications · 2025Article
- Quantifying the impact of genetic mutations on enhancer dynamics.bioRxiv : the preprint server for biology · 2025Article
- Applications of high-throughput reporter assays to gene regulation studies.Current opinion in structural biology · 2025Review
- Adverse gestational environment configures a subpopulation of ventral dentate granule cells for recruitment to drive innate anxiety.Cell reports · 2025Article
- Article
- Article
- Modeling and designing enhancers by introducing and harnessing transcription factor binding units.Nature communications · 2025Article
- Computational analysis of congenital heart disease associated SNPs: unveiling their impact on the gene regulatory system.BMC genomics · 2025Article
- Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.Developmental cell · 2025Article
- Active learning of enhancers and silencers in the developing neural retina.Cell systems · 2025Article
- Comprehensive analysis of computational approaches in plant transcription factors binding regions discovery.Heliyon · 2024Article
- Genetic Variations in theCells · 2024Article
51 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Enhancers regulate gene expression through the binding of sequence-specific transcription factors (TFs) to cognate motifs. Various features influence TF binding and enhancer function-including the chromatin state of the genomic locus, the affinities of the binding site, the activity of the bound TFs, and interactions among TFs. However, the precise nature and relative contributions of these features remain unclear. Here, we used massively parallel reporter assays (MPRAs) involving 32,115 natural and synthetic enhancers, together with high-throughput in vivo binding assays, to systematically dissect the contribution of each of these features to the binding and activity of genomic regulatory elements that contain motifs for PPARγ, a TF that serves as a key regulator of adipogenesis. We show that distinct sets of features govern PPARγ binding vs. enhancer activity. PPARγ binding is largely governed by the affinity of the specific motif site and higher-order features of the larger genomic locus, such as chromatin accessibility. In contrast, the enhancer activity of PPARγ binding sites depends on varying contributions from dozens of TFs in the immediate vicinity, including interactions between combinations of these TFs. Different pairs of motifs follow different interaction rules, including subadditive, additive, and superadditive interactions among specific classes of TFs, with both spatially constrained and flexible grammars. Our results provide a paradigm for the systematic characterization of the genomic features underlying regulatory elements, applicable to the design of synthetic regulatory elements or the interpretation of human genetic variation.
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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.