ArticleScience advances2020
Intrinsic disorder controls two functionally distinct dimers of the master transcription factor PU.1.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Differential conformational expansion of NUP98-HOXA9 oncoprotein from nanosized assemblies to macrophases.Nature communications · 2025Article
- Single-molecule methods for characterizing receptor dimers reveal metastable opioid receptor homodimers that induce functional modulation.Nature communications · 2025Article
- Cell-cycle-related transcriptional factor DLX4: a novel prognostic biomarker and potential therapeutic target in colorectal cancer.Cancer cell international · 2025Article
- Versatile roles of disordered transcription factor effector domains in transcriptional regulation.The FEBS journal · 2025Review
- Design of a light and CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The conformation of FOXM1 homodimers in vivo is crucial for regulating transcriptional activities.Nucleic acids research · 2024Article
- Dissection of integrated readout reveals the structural thermodynamics of DNA selection by transcription factors.Structure (London, England : 1993) · 2024Article
- DNA selection by the master transcription factor PU.1.Cell reports · 2023Article
- Carm1-arginine methylation of the transcription factor C/EBPα regulates transdifferentiation velocity.eLife · 2023Article
- A pioneer factor locally opens compacted chromatin to enable targeted ATP-dependent nucleosome remodeling.Nature structural & molecular biology · 2023Article
- Article
- The Non-continuum Nature of Eukaryotic Transcriptional Regulation.Advances in experimental medicine and biology · 2022Article
- Logic and lineage impacts on functional transcription factor deployment for T-cell fate commitment.Biophysical journal · 2021Review
- Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients.The Journal of experimental medicine · 2021Article
- Asymmetric Conservation within Pairs of Co-Occurred Motifs Mediates Weak Direct Binding of Transcription Factors in ChIP-Seq Data.International journal of molecular sciences · 2020Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Transcription factors comprise a major reservoir of conformational disorder in the eukaryotic proteome. The hematopoietic master regulator PU.1 presents a well-defined model of the most common configuration of intrinsically disordered regions (IDRs) in transcription factors. We report that the structured DNA binding domain (DBD) of PU.1 regulates gene expression via antagonistic dimeric states that are reciprocally controlled by cognate DNA on the one hand and by its proximal anionic IDR on the other. The two conformers are mediated by distinct regions of the DBD without structured contributions from the tethered IDRs. Unlike DNA-bound complexes, the unbound dimer is markedly destabilized. Dimerization without DNA is promoted by progressive phosphomimetic substitutions of IDR residues that are phosphorylated in immune activation and stimulated by anionic crowding agents. These results suggest a previously unidentified, nonstructural role for charged IDRs in conformational control by mitigating electrostatic penalties that would mask the interactions of highly cationic DBDs.
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