ArticleMolecular cell2025
A mechanism of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence.
Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- The Mediator complex: co-transcriptional regulation and beyond.RNA biology · 2026Review
- The molecular basis of transcription initiation by RNA polymerase II.Nature reviews. Molecular cell biology · 2026Review
- Nonlinearities and Switch-Like Behavior in Gene Expression: From Genetics to Biochemistry and Back.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- AID self-assembly and multistranded DNA binding drive synapsis in class switch recombination.Nucleic acids research · 2026Article
- ELOF1 is a core component of the promoter-proximal paused RNA polymerase II complex.bioRxiv : the preprint server for biology · 2026Article
- Density transitions in the regulation of transcription.Molecular cell · 2026Review
- Real-time visualization of reconstituted transcription reveals RNAPII activation mechanisms at single promoters.Cell reports · 2025Article
- Short activation domains control chromatin association of transcription factors.bioRxiv : the preprint server for biology · 2025Article
- Real-time visualization of reconstituted transcription reveals RNA polymerase II activation mechanisms at single promoters.bioRxiv : the preprint server for biology · 2025Article
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Abstract
Transcription activators trigger transcript production by RNA polymerase II (RNAPII) via the Mediator coactivator complex. Here, the dynamics of activator, Mediator, and RNAPII binding at promoter DNA were analyzed using multi-wavelength single-molecule microscopy of fluorescently labeled proteins in budding yeast nuclear extract. Binding of Mediator and RNAPII to the template required an activator and an upstream activating sequence (UAS) but not a core promoter. While Mediator and RNAPII sometimes bind as a pre-formed complex, more commonly Mediator binds first and subsequently recruits RNAPII to form a pre-initiation complex precursor (pre-PIC) tethered to activators on the UAS. Interestingly, Mediator occupancy has a highly non-linear response to activator concentration, and fluorescence intensity measurements show that Mediator preferentially associates with templates having at least two activators bound. Statistical mechanical modeling suggests this "synergy" is not due to cooperative binding between activators but instead occurs when multiple DNA-bound activator molecules simultaneously interact with a single Mediator.
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