ArticleThe Journal of biological chemistry2011
Transient-state kinetic analysis of transcriptional activator·DNA complexes interacting with a key coactivator.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- A mechanism of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence.Molecular cell · 2025Article
- Structural basis of a transcription pre-initiation complex on a divergent promoter.Molecular cell · 2023Article
- MED15 prion-like domain forms a coiled-coil responsible for its amyloid conversion and propagation.Communications biology · 2021Article
- Collision-Induced Unfolding Reveals Unique Fingerprints for Remote Protein Interaction Sites in the KIX Regulation Domain.Journal of the American Society for Mass Spectrometry · 2019Article
- Conservation of coactivator engagement mechanism enables small-molecule allosteric modulators.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Discovery of Enzymatic Targets of Transcriptional Activators via in Vivo Covalent Chemical Capture.Journal of the American Chemical Society · 2016Article
- Analytical methods for kinetic studies of biological interactions: A review.Journal of pharmaceutical and biomedical analysis · 2015Review
- Dissecting allosteric effects of activator-coactivator complexes using a covalent small molecule ligand.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- DNA Methylation at the Novel CpG Sites in the Promoter of MED15/PCQAP Gene as a Biomarker for Head and Neck Cancers.Biomarker insights · 2014Article
- Small molecule probes to target the human Mediator complex.Israel journal of chemistry · 2013Article
- Conserved versatile master regulators in signalling pathways in response to stress in plants.AoB PLANTS · 2013Review
- Transient kinetic analysis of USP2-catalyzed deubiquitination reveals a conformational rearrangement in the K48-linked diubiquitin substrate.Biochemistry · 2012Article
- Sekikaic acid and lobaric acid target a dynamic interface of the coactivator CBP/p300.Angewandte Chemie (International ed. in English) · 2012Article
- Interactions between DNA, transcriptional regulator Dreb2a and the Med25 mediator subunit from Arabidopsis thaliana involve conformational changes.Nucleic acids research · 2012Article
- Caught in the act: covalent cross-linking captures activator-coactivator interactions in vivo.ACS chemical biology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Several lines of evidence suggest that the prototypical amphipathic transcriptional activators Gal4, Gcn4, and VP16 interact with the key coactivator Med15 (Gal11) during transcription initiation despite little sequence homology. Recent cross-linking data further reveal that at least two of the activators utilize the same binding surface within Med15 for transcriptional activation. To determine whether these three activators use a shared binding mechanism for Med15 recruitment, we characterized the thermodynamics and kinetics of Med15·activator·DNA complex formation by fluorescence titration and stopped-flow techniques. Combination of each activator·DNA complex with Med15 produced biphasic time courses. This is consistent with a minimum two-step binding mechanism composed of a bimolecular association step limited by diffusion, followed by a conformational change in the Med15·activator·DNA complex. Furthermore, the equilibrium constant for the conformational change (K(2)) correlates with the ability of an activator to stimulate transcription. VP16, the most potent of the activators, has the largest K(2) value, whereas Gcn4, the least potent, has the smallest value. This correlation is consistent with a model in which transcriptional activation is regulated at least in part by the rearrangement of the Med15·activator·DNA ternary complex. These results are the first detailed kinetic characterization of the transcriptional activation machinery and provide a framework for the future design of potent transcriptional activators.
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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.