ArticleThe Journal of biological chemistry2013
Mediator complex recruits epigenetic regulators via its two cyclin-dependent kinase subunits to repress transcription of immune response genes.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 75 citations in OpenAlex.
- The Mediator complex: co-transcriptional regulation and beyond.RNA biology · 2026Review
- The Role of Transcriptional and Atypical Cyclin-Dependent Protein Kinases in Melanoma.Cancers · 2026Review
- Review
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Remodeling the Epigenome Through Meditation: Effects on Brain, Body, and Well-being.Sub-cellular biochemistry · 2025Review
- Differential roles of regulatory T cells in acute respiratory infections.The Journal of clinical investigation · 2023Review
- C/EBPβ deficiency enhances the keratinocyte innate immune response to direct activators of cytosolic pattern recognition receptors.Innate immunity · 2023Article
- Protein arginine methylation in transcription and epigenetic regulation.Frontiers in epigenetics and epigenomics · 2023Review
- MEDIATOR SUBUNIT17 integrates jasmonate and auxin signaling pathways to regulate thermomorphogenesis.Plant physiology · 2022Article
- Changes in the expression of inflammatory and epigenetic-modulatory genes after an intensive meditation retreat.Comprehensive psychoneuroendocrinology · 2022Article
- Epigenetic Control of Regulatory T Cell Stability and Function: Implications for Translation.Frontiers in immunology · 2022Review
- Dissection of two routes to naïve pluripotency using different kinase inhibitors.Nature communications · 2021Article
- Transcriptional regulation by methyltransferases and their role in the heart: highlighting novel emerging functionality.American journal of physiology. Heart and circulatory physiology · 2020Review
- The CYCLIN-DEPENDENT KINASE Module of the Mediator Complex Promotes Flowering and Reproductive Development in Pea.Plant physiology · 2020Article
- CDK8-Novel Therapeutic Opportunities.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Disruption of cardiac Med1 inhibits RNA polymerase II promoter occupancy and promotes chromatin remodeling.American journal of physiology. Heart and circulatory physiology · 2019Article
- Targeting PRMT5 Activity Inhibits the Malignancy of Hepatocellular Carcinoma by Promoting the Transcription of HNF4α.Theranostics · 2019Article
- Review
- Mediator complex component MED13 regulates zygotic genome activation and is required for postimplantation development in the mouse.Biology of reproduction · 2018Article
- Modulating the expression of Chtop, a versatile regulator of gene-specific transcription and mRNA export.RNA biology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Mediator complex (Mediator) plays pivotal roles in activating transcription by RNA polymerase II, but relatively little is known about its roles in repression. Here, we identified the histone arginine methyltransferase PRMT5 and WD repeat protein 77/methylosome protein 50 (WDR77/MEP50) as Mediator cyclin-dependent kinase (CDK)-interacting proteins and studied the roles of PRMT5 in the transcriptional regulation of CCAAT enhancer-binding protein (C/EBP) β target genes. First, we purified CDK8- and CDK19-containing complexes from HeLa nuclear extracts and subjected these purified complexes to mass spectrometric analyses. These experiments revealed that two Mediator CDKs, CDK8 and CDK19, individually interact with PRMT5 and WDR77, and their interactions with PRMT5 cause transcriptional repression of C/EBPβ target genes by regulating symmetric dimethylation of histone H4 arginine 3 (H4R3me2s) in the promoter regions of those genes. Furthermore, the recruitment of the DNA methyltransferase DNMT3A correlated with H4R3 dimethylation potentially leading to DNA methylation at the promoter proximal region and tight inhibition of preinitiation complex formation. In vertebrates, C/EBPβ regulates many genes involved in immune responses and cell differentiation. These findings shed light on the molecular mechanisms of the repressive roles of Mediator CDKs in transcription of C/EBPβ target genes and might provide clues that enable future studies of the functional associations between Mediators and epigenetic regulation.
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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.