ArticleMolecular cell2021
Cooperative binding between distant transcription factors is a hallmark of active enhancers.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed.
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- Conserved noncoding sequence-9 regulates NFATc1-mediated IL-10 expression in B cells to control inflammatory responses.Science advances · 2026Article
- Coordinated Temporal Dynamics of Glucocorticoid Receptor Binding and Chromatin Landscape Drive Transcriptional Regulation.bioRxiv : the preprint server for biology · 2026Article
- Transcription factor collaboration enables precise T cell state engineering.bioRxiv : the preprint server for biology · 2026Article
- Interplay between circadian and other transcription factors-Implications for cycling transcriptome reprogramming.FEBS letters · 2026Review
- A comprehensive evaluation of self-attention for detecting regulatory feature interactions.NAR genomics and bioinformatics · 2026Article
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- SMTrackR: an R/Bioconductor package for mapping protein binding at individual DNA molecules.Bioinformatics advances · 2026Article
- IKAROS Gene Regulatory Network Reveal ERG as a Vulnerability in B-cell Acute Lymphoblastic Leukemia.bioRxiv : the preprint server for biology · 2025Article
- Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells.Genome research · 2025Article
- Loop Catalog: a comprehensive HiChIP database of human and mouse samples.Genome biology · 2025Article
- Pioneering new enhancers by GATA3: role of facilitating transcription factors and chromatin remodeling.Nucleic acids research · 2025Article
- Transcriptional induction by ecdysone in Drosophila salivary glands involves an increase in chromatin accessibility and acetylation.Nucleic acids research · 2025Article
- Inhibition of triglyceride metabolism-associated enhancers alters lipid deposition during adipocyte differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Genetic coupling of enhancer activity and connectivity in gene expression control.Nature communications · 2025Article
- ChromBPNet: bias factorized, base-resolution deep learning models of chromatin accessibility reveal cis-regulatory sequence syntax, transcription factor footprints and regulatory variants.bioRxiv : the preprint server for biology · 2025Article
- NetREm: Network Regression Embeddings reveal cell-type transcription factor coordination for gene regulation.Bioinformatics advances · 2025Article
- The RNA Revolution in the Central Molecular Biology Dogma Evolution.International journal of molecular sciences · 2024Review
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Abstract
Enhancers harbor binding motifs that recruit transcription factors (TFs) for gene activation. While cooperative binding of TFs at enhancers is known to be critical for transcriptional activation of a handful of developmental enhancers, the extent of TF cooperativity genome-wide is unknown. Here, we couple high-resolution nuclease footprinting with single-molecule methylation profiling to characterize TF cooperativity at active enhancers in the Drosophila genome. Enrichment of short micrococcal nuclease (MNase)-protected DNA segments indicates that the majority of enhancers harbor two or more TF-binding sites, and we uncover protected fragments that correspond to co-bound sites in thousands of enhancers. From the analysis of co-binding, we find that cooperativity dominates TF binding in vivo at the majority of active enhancers. Cooperativity is highest between sites spaced 50 bp apart, indicating that cooperativity occurs without apparent protein-protein interactions. Our findings suggest nucleosomes promoting cooperativity because co-binding may effectively clear nucleosomes and promote enhancer function.
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