ArticleThe EMBO journal2008
Cooperative activity of cdk8 and GCN5L within Mediator directs tandem phosphoacetylation of histone H3.
Article in The EMBO journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 96 citations in OpenAlex.
- The Mediator complex: co-transcriptional regulation and beyond.RNA biology · 2026Review
- Cyclin C promotes development and progression of B-cell acute lymphoblastic leukemia by counteracting p53-mediated stress responses.Haematologica · 2025Article
- H3K14: A histone site closely related to diseases.Journal of Cancer · 2025Review
- What's all the phos about? Insights into the phosphorylation state of the RNA polymerase II C-terminal domainRSC chemical biology · 2021Review
- Simplicity is the Ultimate Sophistication-Crosstalk of Post-translational Modifications on the RNA Polymerase II.Journal of molecular biology · 2021Review
- Rebelled epigenome: histone H3S10 phosphorylation and H3S10 kinases in cancer biology and therapy.Clinical epigenetics · 2020Review
- Dissecting the Pol II transcription cycle and derailing cancer with CDK inhibitors.Nature chemical biology · 2020Review
- Partitioning of cancer therapeutics in nuclear condensates.Science (New York, N.Y.) · 2020Article
- Cyclin-Dependent Kinases 8 and 19 Regulate Host Cell Metabolism during Dengue Virus Serotype 2 Infection.Viruses · 2020Article
- Article
- Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes.Molecular cell · 2019Article
- Targeting transcriptional machinery to inhibit enhancer-driven gene expression in heart failure.Heart failure reviews · 2019Review
- Pol II phosphorylation regulates a switch between transcriptional and splicing condensates.Nature · 2019Article
- Regulatory functions of the Mediator kinases CDK8 and CDK19.Transcription · 2019Review
- Transcriptional Silencing of MCL-1 Through Cyclin-Dependent Kinase Inhibition in Acute Myeloid Leukemia.Frontiers in oncology · 2019Review
- Article
- Development of Highly Potent and Selective Steroidal Inhibitors and Degraders of CDK8.ACS medicinal chemistry letters · 2018Article
- Phosphorylation of EZH2 by AMPK Suppresses PRC2 Methyltransferase Activity and Oncogenic Function.Molecular cell · 2018Article
- Inhibitors of cyclin-dependent kinases as cancer therapeutics.Pharmacology & therapeutics · 2017Review
- The CDK8 Complex and Proneural Proteins Together Drive Neurogenesis from a Mesodermal Lineage.Current biology : CB · 2017Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The human Mediator complex is generally required for expression of protein-coding genes. Here, we show that the GCN5L acetyltransferase stably associates with Mediator together with the TRRAP polypeptide. Yet, contrary to expectations, TRRAP/GCN5L does not associate with the transcriptionally active core Mediator but rather with Mediator that contains the cdk8 subcomplex. Consequently, this derivative 'T/G-Mediator' complex does not directly activate transcription in a reconstituted human transcription system. However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo. Moreover, cdk8 knockdown causes substantial reduction of global H3 phosphoacetylation, suggesting that T/G-Mediator is a major regulator of this H3 mark. Cooperative H3 modification provides a mechanistic basis for GCN5L association with cdk8-Mediator and also identifies a biochemical means by which cdk8 can indirectly activate gene expression. Indeed our results suggest that T/G-Mediator directs early events-such as modification of chromatin templates-in transcriptional activation.
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What OpenQuestion holds
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.