ArticleNucleic acids research2024
Massively parallel binding assay (MPBA) reveals limited transcription factor binding cooperativity, challenging models of specificity.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- A transcription factor by any other name - function beyond DNA binding and transactivation.EMBO reports · 2026Review
- Nonlinearities and Switch-Like Behavior in Gene Expression: From Genetics to Biochemistry and Back.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Spatially resolved profiling of steroid nuclear receptors reveals a role for the disordered N-terminal domains in genome targeting and AP-1 interaction.Genome research · 2026Article
- Thermal Processing Techniques Differentially Modulate Phytochemicals, Antioxidant Potential, and Genoprotective Effects of Kale (Plants (Basel, Switzerland) · 2025Article
- Reporter CRISPR screens decipher cis-regulatory and trans-regulatory principles at the Xist locus.Nature structural & molecular biology · 2025Article
- The transcriptomics of phenotypic nonspecificity in Drosophila melanogaster.G3 (Bethesda, Md.) · 2025Article
- The Environment-Dependent Regulatory Landscape of thebioRxiv : the preprint server for biology · 2025Article
- Article
- An RNA-centric view of transcription and genome organization.Molecular cell · 2024Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
DNA-binding domains (DBDs) within transcription factors (TFs) recognize short sequence motifs that are highly abundant in genomes. In vivo, TFs bind only a small subset of motif occurrences, which is often attributed to the cooperative binding of interacting TFs at proximal motifs. However, large-scale testing of this model is still lacking. Here, we describe a novel method allowing parallel measurement of TF binding to thousands of designed sequences within yeast cells and apply it to quantify the binding of dozens of TFs to libraries of regulatory regions containing clusters of binding motifs, systematically mutating all motif combinations. With few exceptions, TF occupancies were well explained by independent binding to individual motifs, with motif cooperation being of only limited effects. Our results challenge the general role of motif combinatorics in directing TF genomic binding and open new avenues for exploring the basis of protein-DNA interactions within cells.
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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.