ArticleCell systems2018
A High-Throughput Mutational Scan of an Intrinsically Disordered Acidic Transcriptional Activation Domain.
Article in Cell systems, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed.
- How do low-complexity domain interactions control transcription?Biochemical Society transactions · 2026Review
- Article
- 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
- Autoinhibition of untimely DNA binding by structural disorder in the full-length peroxisome proliferator-activated receptors (PPARs).Nature communications · 2026Article
- Article
- 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
- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- 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
- Article
- Molecular grammars of predicted intrinsically disordered regions that span the human proteome.Cell · 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
- Evolutionary discovery and characterization of fungal transcriptional activators using active learning.bioRxiv : the preprint server for biology · 2025Article
- Interpretable biophysical neural networks of transcriptional activation domains separate roles of protein abundance and coactivator binding.bioRxiv : the preprint server for biology · 2025Article
- PIF4-mediated thermomorphogenesis relies on its oligomerization ability, not DNA-binding or transactivation activity.Research square · 2025Article
- Short activation domains control chromatin association of transcription factors.bioRxiv : the preprint server for biology · 2025Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Transcriptional activation domains are essential for gene regulation, but their intrinsic disorder and low primary sequence conservation have made it difficult to identify the amino acid composition features that underlie their activity. Here, we describe a rational mutagenesis scheme that deconvolves the function of four activation domain sequence features-acidity, hydrophobicity, intrinsic disorder, and short linear motifs-by quantifying the activity of thousands of variants in vivo and simulating their conformational ensembles using an all-atom Monte Carlo approach. Our results with a canonical activation domain from the Saccharomyces cerevisiae transcription factor Gcn4 reconcile existing observations into a unified model of its function: the intrinsic disorder and acidic residues keep two hydrophobic motifs from driving collapse. Instead, the most-active variants keep their aromatic residues exposed to the solvent. Our results illustrate how the function of intrinsically disordered proteins can be revealed by high-throughput rational mutagenesis.
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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.