ArticleeLife2021
Simple biochemical features underlie transcriptional activation domain diversity and dynamic, fuzzy binding to Mediator.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed.
- Type III effectors of symbiotic Rhizobia include diverse predicted transcriptional and post-transcriptional modulators.PLoS biology · 2026Article
- Interpretable biophysical neural networks of transcriptional activation domains separate roles of protein abundance and coactivator binding.Cell systems · 2026Article
- Autoinhibition of untimely DNA binding by structural disorder in the full-length peroxisome proliferator-activated receptors (PPARs).Nature communications · 2026Article
- Article
- Pioneer-factor activity requires stable chromatin occupancy mediated by both sequence-specific binding and disordered protein domains.Science advances · 2026Article
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- Generative design of intrinsically disordered protein regions with IDiom.bioRxiv : the preprint server for biology · 2026Article
- A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform.Science (New York, N.Y.) · 2026Article
- Oligomerization-competent PIF4 drives thermomorphogenesis through functional redundancy in transactivation and DNA binding.Nature communications · 2026Article
- Evolutionary turnover of key amino acids explains conservation of function without conservation of sequence in transcriptional activation domains.PLoS genetics · 2026Article
- Mechanism of interaction between the transactivation domain of N-myc and the DNA-binding surface of TFIIIC5.Nucleic acids research · 2026Article
- Density transitions in the regulation of transcription.Molecular cell · 2026Review
- Sequence and chemical specificity define the functional landscape of intrinsically disordered regions.Nature cell biology · 2026Article
- Article
- Enhancer Trajectories in Lineage Commitment: Regulatory Logic of States and Cooperation.Biomolecules · 2026Review
- Role of PBAF and Mediator kinase module in the RELA-dependent activation ofFrontiers in immunology · 2026Article
- Multiplexed profiling of transcriptional regulators in plant cells.Nature biotechnology · 2025Article
- Combinatorial protein engineering identifies potent CRISPR activators with reduced toxicity.Nature communications · 2025Article
- Differential conformational expansion of NUP98-HOXA9 oncoprotein from nanosized assemblies to macrophases.Nature communications · 2025Article
- A mechanism of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence.Molecular cell · 2025Article
50 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
Gene activator proteins comprise distinct DNA-binding and transcriptional activation domains (ADs). Because few ADs have been described, we tested domains tiling all yeast transcription factors for activation in vivo and identified 150 ADs. By mRNA display, we showed that 73% of ADs bound the Med15 subunit of Mediator, and that binding strength was correlated with activation. AD-Mediator interaction in vitro was unaffected by a large excess of free activator protein, pointing to a dynamic mechanism of interaction. Structural modeling showed that ADs interact with Med15 without shape complementarity ('fuzzy' binding). ADs shared no sequence motifs, but mutagenesis revealed biochemical and structural constraints. Finally, a neural network trained on AD sequences accurately predicted ADs in human proteins and in other yeast proteins, including chromosomal proteins and chromatin remodeling complexes. These findings solve the longstanding enigma of AD structure and function and provide a rationale for their role in biology.
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