ArticleNature cell biology2024
An activity-specificity trade-off encoded in human transcription factors.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Spatially resolved profiling of steroid nuclear receptors reveals a role for the disordered N-terminal domains in genome targeting and AP-1 interaction.Genome research · 2026Article
- From chromosomal protein disorder to chromatin phase separation.Epigenetics & chromatin · 2026Review
- Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule.Science advances · 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
- Biomolecular condensates as cellular memory modules: Thermodynamic principles and plant stress adaptation.Biophysical journal · 2026Review
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- Real-time visualization of reconstituted transcription reveals RNAPII activation mechanisms at single promoters.Cell reports · 2025Article
- Enhanced Activities of OCT4 and SOX2 Promote Epigenetic Reprogramming by Shortening G1 Phase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Article
- Biomolecular condensates in immune cell fate.Nature reviews. Immunology · 2025Review
- Versatile roles of disordered transcription factor effector domains in transcriptional regulation.The FEBS journal · 2025Review
- Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation.Nature communications · 2025Article
- Functional specificity in biomolecular condensates revealed by genetic complementation.Nature reviews. Genetics · 2025Review
- Transcription regulation by biomolecular condensates.Nature reviews. Molecular cell biology · 2025Review
- Biomolecular condensation of human IDRs initiates endogenous transcription via intrachromosomal looping or high-density promoter localization.Nucleic acids research · 2025Article
- Molecular determinants of condensate composition.Molecular cell · 2025Review
- Real-time visualization of reconstituted transcription reveals RNA polymerase II activation mechanisms at single promoters.bioRxiv : the preprint server for biology · 2025Article
- Built to be imperfect.Nature cell biology · 2024Article
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14 authors.
Funding
Abstract
Transcription factors (TFs) control specificity and activity of gene transcription, but whether a relationship between these two features exists is unclear. Here we provide evidence for an evolutionary trade-off between the activity and specificity in human TFs encoded as submaximal dispersion of aromatic residues in their intrinsically disordered protein regions. We identified approximately 500 human TFs that encode short periodic blocks of aromatic residues in their intrinsically disordered regions, resembling imperfect prion-like sequences. Mutation of periodic aromatic residues reduced transcriptional activity, whereas increasing the aromatic dispersion of multiple human TFs enhanced transcriptional activity and reprogramming efficiency, promoted liquid-liquid phase separation in vitro and more promiscuous DNA binding in cells. Together with recent work on enhancer elements, these results suggest an important evolutionary role of suboptimal features in transcriptional control. We propose that rational engineering of amino acid features that alter phase separation may be a strategy to optimize TF-dependent processes, including cellular reprogramming.
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