ArticleCell systems2022
Directed mutational scanning reveals a balance between acidic and hydrophobic residues in strong human activation domains.
Article in Cell systems, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed.
- How do low-complexity domain interactions control transcription?Biochemical Society transactions · 2026Review
- A transcription factor by any other name - function beyond DNA binding and transactivation.EMBO reports · 2026Review
- Interpretable biophysical neural networks of transcriptional activation domains separate roles of protein abundance and coactivator binding.Cell systems · 2026Article
- Acidic transcription factors position the genome at nuclear speckles through transcription-dependent and -independent mechanisms.Molecular cell · 2026Article
- Autoinhibition of untimely DNA binding by structural disorder in the full-length peroxisome proliferator-activated receptors (PPARs).Nature communications · 2026Article
- Article
- Opposing roles of serine and charge in IDR condensate miscibility.Nature chemical biology · 2026Article
- Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding.Protein science : a publication of the Protein Society · 2026Article
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- Isoform-specific cofactor recruitment through the intrinsically disordered N-terminus of p63 underlies differential transcriptional activities.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
- Human pumilio proteins use fuzzy multivalent hydrophobic interactions to recruit the CCR4-NOT deadenylase complex to repress mRNAs.The Journal of biological chemistry · 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
- Sequence and chemical specificity define the functional landscape of intrinsically disordered regions.Nature cell biology · 2026Article
- Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding.bioRxiv : the preprint server for biology · 2026Article
- Article
- Molecular grammars of predicted intrinsically disordered regions that span the human proteome.Cell · 2026Article
- Linker Length and Composition within Disordered Binding Motifs Modulates the Avidity and Reversibility of a Multivalent Protein Interaction Switch.Journal of molecular biology · 2025Article
20 more citing papers are in PubMed but not listed here.
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6 authors.
Funding
Abstract
Acidic activation domains are intrinsically disordered regions of the transcription factors that bind coactivators. The intrinsic disorder and low evolutionary conservation of activation domains have made it difficult to identify the sequence features that control activity. To address this problem, we designed thousands of variants in seven acidic activation domains and measured their activities with a high-throughput assay in human cell culture. We found that strong activation domain activity requires a balance between the number of acidic residues and aromatic and leucine residues. These findings motivated a predictor of acidic activation domains that scans the human proteome for clusters of aromatic and leucine residues embedded in regions of high acidity. This predictor identifies known activation domains and accurately predicts previously unidentified ones. Our results support a flexible acidic exposure model of activation domains in which the acidic residues solubilize hydrophobic motifs so that they can interact with coactivators. A record of this paper's transparent peer review process is included in the supplemental information.
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