ArticleMolecular cell2024
Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 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
- A phosphatidic acid-based retrograde signaling pathway responsive to abiotic stress in Arabidopsis.The Plant journal : for cell and molecular biology · 2026Article
- Vitamin D3 ameliorates R-loop-induced replication stress and chromosomal instability in MED12-mutant uterine fibroids.Scientific reports · 2026Article
- Non-canonical subunit functions in multiprotein complexes: insights from the Mediator complex.Biochemical Society transactions · 2026Review
- Article
- Vitamin D3 ameliorates R-loop-induced replication stress and chromosomal instability in MED12-mutant uterine fibroids.Research square · 2026Article
- Role of PBAF and Mediator kinase module in the RELA-dependent activation ofFrontiers in immunology · 2026Article
- Nucleolar MED19 regulates 2'-O-methylation of rRNA in supporting cancer cell growth.Nucleic acids research · 2025Article
- Mediator Kinase Inhibitor Selectivity and Activity in Colorectal Cancer.ACS chemical biology · 2025Article
- The Mediator Kinase Module regulates cell cycle re-entry and transcriptional responses following DNA damage.bioRxiv : the preprint server for biology · 2025Article
- Review
- Structural basis of human Mediator recruitment by the phosphorylated transcription factor Elk-1.Nature communications · 2025Article
- Mediator kinase inhibition drives myometrial stem cell differentiation and the uterine fibroid phenotype through super-enhancer reprogramming.Journal of molecular medicine (Berlin, Germany) · 2025Article
- A Protocol to Purify Human Mediator Complex From Freestyle 293-F Cells.Bio-protocol · 2025Article
- Mediator kinase inhibition drives myometrial stem cell differentiation and the uterine fibroid phenotype through super-enhancer reprogramming.Research square · 2024Article
- Subunits Med12 and Med13 of Mediator Cooperate with Subunits SAYP and Bap170 of SWI/SNF in Active Transcription inInternational journal of molecular sciences · 2024Article
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14 authors.
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Abstract
The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex formation in a manner repressed by the CKM through mechanisms presently unknown. Herein, we report cryoelectron microscopy structures of the complete human Mediator and its CKM. The CKM binds to multiple regions on cMED through both MED12 and MED13, including a large intrinsically disordered region (IDR) in the latter. MED12 and MED13 together anchor the CKM to the cMED hook, positioning CDK8 downstream and proximal to the transcription start site. Notably, the MED13 IDR obstructs the recruitment of RNA Pol II/MED26 onto cMED by direct occlusion of their respective binding sites, leading to functional repression of cMED-dependent transcription. Combined with biochemical and functional analyses, these structures provide a conserved mechanistic framework to explain the basis for CKM-mediated repression of cMED function.
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