ArticleMolecular systems biology2018
High-throughput discovery of functional disordered regions: investigation of transactivation domains.
Article in Molecular systems biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 188 citations in OpenAlex.
- Interpretable biophysical neural networks of transcriptional activation domains separate roles of protein abundance and coactivator binding.Cell systems · 2026Article
- Article
- No Time to Fold: Intrinsically Disordered Microproteins in Action.Biochemistry · 2026Review
- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- Evolutionary turnover of key amino acids explains conservation of function without conservation of sequence in transcriptional activation domains.PLoS genetics · 2026Article
- Sequence and chemical specificity define the functional landscape of intrinsically disordered regions.Nature cell biology · 2026Article
- 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
- Interpretable biophysical neural networks of transcriptional activation domains separate roles of protein abundance and coactivator binding.bioRxiv : the preprint server for biology · 2025Article
- Reconciling competing models on the roles of condensates and soluble complexes in transcription factor function.Molecular cell · 2025Article
- Hierarchy in regulator interactions with distant transcriptional activation domains empowers rheostatic regulation.Protein science : a publication of the Protein Society · 2025Article
- Intrinsically disordered regions as facilitators of the transcription factor target search.Nature reviews. Genetics · 2025Review
- The intrinsically disordered AB region: a key modulator of the molecular properties of human RXRγ.Cell communication and signaling : CCS · 2025Article
- Sequence-based prediction of intermolecular interactions driven by disordered regions.Science (New York, N.Y.) · 2025Article
- Article
- Revisiting the model for coactivator recruitment: Med15 can select its target sites independent of promoter-bound transcription factors.Nucleic acids research · 2024Article
- High-throughput affinity measurements of direct interactions between activation domains and co-activators.bioRxiv : the preprint server for biology · 2024Article
- Direct prediction of intermolecular interactions driven by disordered regions.bioRxiv : the preprint server for biology · 2024Article
- A Lipopeptidomimetic of Transcriptional Activation Domains Selectively Disrupts the Coactivator Med25 Protein-Protein Interactions.Angewandte Chemie (International ed. in English) · 2024Article
- Predicting transcriptional activation domain function using Graph Neural Networks.bioRxiv : the preprint server for biology · 2024Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Over 40% of proteins in any eukaryotic genome encode intrinsically disordered regions (IDRs) that do not adopt defined tertiary structures. Certain IDRs perform critical functions, but discovering them is non-trivial as the biological context determines their function. We present IDR-Screen, a framework to discover functional IDRs in a high-throughput manner by simultaneously assaying large numbers of DNA sequences that code for short disordered sequences. Functionality-conferring patterns in their protein sequence are inferred through statistical learning. Using yeast HSF1 transcription factor-based assay, we discovered IDRs that function as transactivation domains (TADs) by screening a random sequence library and a designed library consisting of variants of 13 diverse TADs. Using machine learning, we find that segments devoid of positively charged residues but with redundant short sequence patterns of negatively charged and aromatic residues are a generic feature for TAD functionality. We anticipate that investigating defined sequence libraries using IDR-Screen for specific functions can facilitate discovering novel and functional regions of the disordered proteome as well as understand the impact of natural and disease variants in disordered segments.
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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.