The Mediator kinase module: an interface between cell signaling and transcription

The Inhibition of CDK8/19 Mediator Kinases Prevents the Development of Resistance to EGFR-Targeting Drugs

(2021) Amanda C. Sharko et al.   Cells

Structure of the human Mediator-bound transcription preinitiation complex

(2021) R. Abdella et al.   SCIENCE

Structure of mammalian Mediator complex reveals Tail module architecture and interaction with a conserved core

(2021) Haiyan Zhao et al.   Nature Communications

Multi-omics analysis reveals contextual tumor suppressive and oncogenic gene modules within the acute hypoxic response

(2021) Zdenek Andrysik et al.   Nature Communications

Somatic and de novo Germline Variants of MEDs in Human Neural Tube Defects

(2021) Tian Tian et al.   Frontiers in Cell and Developmental Biology

Seeing beyond the limit: a guide to choosing the right super resolution microscopy technique

(2021) Jessica Valli et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Cdk8 kinase module regulates interaction of the Mediator complex with RNA polymerase II

(2021) Sara Osman et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Towards a ‘Spot On’ Understanding of Transcription in the Nucleus

(2021) Simona Patange et al.   JOURNAL OF MOLECULAR BIOLOGY

Structure of the human Mediator–RNA polymerase II pre-initiation complex

(2021) Srinivasan Rengachari et al.   NATURE

Structures of the human Mediator and Mediator-bound preinitiation complex

(2021) Xizi Chen et al.   SCIENCE

Dissection of two routes to naïve pluripotency using different kinase inhibitors

(2021) Ana Martinez-Val et al.   Nature Communications

Spatiotemporal coordination of transcription preinitiation complex assembly in live cells

(2021) Vu Q. Nguyen et al.   MOLECULAR CELL

Testing the super-enhancer concept

(2021) Gerd A. Blobel et al.   NATURE REVIEWS GENETICS

MED12 and BRD4 cooperate to sustain cancer growth upon loss of mediator kinase

(2021) Dhanya Sooraj et al.   MOLECULAR CELL

Termination of non‐coding transcription in yeast relies on both an RNA Pol II CTD interaction domain and a CTD‐mimicking region in Sen1

(2020) Zhong Han et al.   EMBO JOURNAL

Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas

(2020) Mthabisi B. Moyo et al.   Nature Communications

De Novo Variants in CDK19 Are Associated with a Syndrome Involving Intellectual Disability and Epileptic Encephalopathy

(2020) Hyung-lok Chung et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Transcription in Living Cells: Molecular Mechanisms of Bursting

(2020) Joseph Rodriguez et al.   Annual Review of Biochemistry

Structure and mechanism of the RNA polymerase II transcription machinery

(2020) Allison C. Schier et al.   GENES & DEVELOPMENT

TFIID Enables RNA Polymerase II Promoter-Proximal Pausing

(2020) Charli B. Fant et al.   MOLECULAR CELL

Enhancer architecture sensitizes cell specific responses to Notch gene dose via a bind and discard mechanism

(2020) Yi Kuang et al.   eLife

Biomolecular Condensates in the Nucleus

(2020) Benjamin R. Sabari et al.   TRENDS IN BIOCHEMICAL SCIENCES

Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases

(2020) Cian J. Lynch et al.   NATURE CELL BIOLOGY

CDK8 Fine-Tunes IL-6 Transcriptional Activities by Limiting STAT3 Resident Time at the Gene Loci

(2020) Jonathan Martinez-Fabregas et al.   Cell Reports

The Cdk8/19-cyclin C transcription regulator functions in genome replication through metazoan Sld7

(2019) Kerstin Köhler et al.   PLOS BIOLOGY

Integrative modeling reveals key chromatin and sequence signatures predicting super-enhancers

(2019) Aziz Khan et al.   Scientific Reports

Promoter-proximal pausing of RNA polymerase II: a nexus of gene regulation

(2019) Leighton Core et al.   GENES & DEVELOPMENT

Metabolic regulation of cell growth and proliferation

(2019) Jiajun Zhu et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

The AP-1 transcriptional complex: Local switch or remote command?

(2019) Fabienne Bejjani et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers

(2019) Laila El Khattabi et al.   CELL

Transcriptional Responses to IFN-γ Require Mediator Kinase-Dependent Pause Release and Mechanistically Distinct CDK8 and CDK19 Functions

(2019) Iris Steinparzer et al.   MOLECULAR CELL

Organization and regulation of gene transcription

(2019) Patrick Cramer   NATURE

Molecular basis and biological function of variability in spatial genome organization

(2019) Elizabeth H. Finn et al.   SCIENCE

Identifying Cancers Impacted by CDK8/19

(2019) Igor B. Roninson et al.   Cells

A kinase-independent role for CDK8 in BCR-ABL1+ leukemia

(2019) Ingeborg Menzl et al.   Nature Communications

Conversion of antigen-specific effector/memory T cells into Foxp3-expressing Treg cells by inhibition of CDK8/19

(2019) Masahiko Akamatsu et al.   Science Immunology

Mediator complex component MED13 regulates zygotic genome activation and is required for postimplantation development in the mouse†,‡

(2018) Yi-Liang Miao et al.   BIOLOGY OF REPRODUCTION

Analysis of Allelic Series with Transcriptomic Phenotypes

(2018) David Angeles-Albores et al.   GENETICS

Enhancer RNA profiling predicts transcription factor activity

(2018) Joseph G. Azofeifa et al.   GENOME RESEARCH

Oncogenic exon 2 mutations in Mediator subunit MED12 disrupt allosteric activation of cyclin C-CDK8/19

(2018) Min Ju Park et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Depletion of Mediator Kinase Module Subunits Represses Superenhancer-Associated Genes in Colon Cancer Cells

(2018) Emilia Kuuluvainen et al.   MOLECULAR AND CELLULAR BIOLOGY

JMJD6 Licenses ERα-Dependent Enhancer and Coding Gene Activation by Modulating the Recruitment of the CARM1/MED12 Co-activator Complex

(2018) Wei-wei Gao et al.   MOLECULAR CELL

Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer

(2018) Anne Serrao et al.   ONCOGENE

Zyxin promotes colon cancer tumorigenesis in a mitotic phosphorylation-dependent manner and through CDK8-mediated YAP activation

(2018) Jiuli Zhou et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment

(2018) Emilia Dimitrova et al.   eLife

Analysis of Allelic Series with Transcriptomic Phenotypes

(2018) David Angeles-Albores et al.   GENETICS

Structure of activated transcription complex Pol II–DSIF–PAF–SPT6

(2018) Seychelle M. Vos et al.   NATURE

Cyclin C directly stimulates Drp1 GTP affinity to mediate stress-induced mitochondrial hyper-fission

(2018) Vidyaramanan Ganesan et al.   MOLECULAR BIOLOGY OF THE CELL

MED12-related XLID disorders are dose-dependent of immediate early genes (IEGs) expression

(2017) Lise-Marie Donnio et al.   HUMAN MOLECULAR GENETICS

A Kinase-Independent Role for Cyclin-Dependent Kinase 19 in p53 Response

(2017) K. Audrey Audetat et al.   MOLECULAR AND CELLULAR BIOLOGY

Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de‐differentiated state

(2017) Mohammad Fallahi‐Sichani et al.   Molecular Systems Biology

Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells

(2017) Liv Johannessen et al.   Nature Chemical Biology

CDK8/19 Mediator kinases potentiate induction of transcription by NFκB

(2017) Mengqian Chen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

CDK8 Kinase Activity Promotes Glycolysis

(2017) Matthew D. Galbraith et al.   Cell Reports

CDK9-dependent RNA polymerase II pausing controls transcription initiation

(2017) Saskia Gressel et al.   eLife

Mediator Kinase Phosphorylation of STAT1 S727 Promotes Growth of Neoplasms With JAK-STAT Activation

(2017) Ioana I. Nitulescu et al.   EBioMedicine

Enhancer Control of Transcriptional Bursting

(2016) Takashi Fukaya et al.   CELL

MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis

(2016) Beatriz Aranda-Orgilles et al.   Cell Stem Cell

P-TEFb regulation of transcription termination factor Xrn2 revealed by a chemical genetic screen for Cdk9 substrates

(2016) Miriam Sansó et al.   GENES & DEVELOPMENT

Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination

(2016) Anne-Sophie Thomas-Claudepierre et al.   JOURNAL OF EXPERIMENTAL MEDICINE

The RNA Polymerase II CTD: The Increasing Complexity of a Low-Complexity Protein Domain

(2016) Célia Jeronimo et al.   JOURNAL OF MOLECULAR BIOLOGY

Mediator Undergoes a Compositional Change during Transcriptional Activation

(2016) Natalia Petrenko et al.   MOLECULAR CELL

Tail and Kinase Modules Differently Regulate Core Mediator Recruitment and Function In Vivo

(2016) Célia Jeronimo et al.   MOLECULAR CELL

ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules

(2016) Haim Ashkenazy et al.   NUCLEIC ACIDS RESEARCH

BET Bromodomain Inhibition Releases the Mediator Complex from Select cis -Regulatory Elements

(2016) Anand S. Bhagwat et al.   Cell Reports

Identification of Mediator Kinase Substrates in Human Cells using Cortistatin A and Quantitative Phosphoproteomics

(2016) Zachary C. Poss et al.   Cell Reports

Set1/COMPASS and Mediator are repurposed to promote epigenetic transcriptional memory

(2016) Agustina D'Urso et al.   eLife

Cdk8deletion in theApcMinmurine tumour model represses EZH2 activity and accelerates tumourigenesis

(2015) Mark L McCleland et al.   JOURNAL OF PATHOLOGY

Mediator kinase inhibition further activates super-enhancer-associated genes in AML

(2015) Henry E. Pelish et al.   NATURE

The selection and function of cell type-specific enhancers

(2015) Sven Heinz et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

(2015) Erik Arner et al.   SCIENCE

CDK8-Cyclin C Mediates Nutritional Regulation of Developmental Transitions through the Ecdysone Receptor in Drosophila

(2015) Xiao-Jun Xie et al.   PLOS BIOLOGY

Looping Back to Leap Forward: Transcription Enters a New Era

(2014) Michael Levine et al.   CELL

Control of Cell Identity Genes Occurs in Insulated Neighborhoods in Mammalian Chromosomes

(2014) Jill M. Dowen et al.   CELL

Med13p prevents mitochondrial fission and programmed cell death in yeast through nuclear retention of cyclin C

(2014) Svetlana Khakhina et al.   MOLECULAR BIOLOGY OF THE CELL

Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

(2014) Nicholas Kwiatkowski et al.   NATURE

Cyclin C is a haploinsufficient tumour suppressor

(2014) Na Li et al.   NATURE CELL BIOLOGY

Heart- and muscle-derived signaling system dependent on MED13 and Wingless controls obesity inDrosophila

(2014) Ji-Hoon Lee et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Uterine Leiomyoma-Linked MED12 Mutations Disrupt Mediator-Associated CDK Activity

(2014) Mikko Turunen et al.   Cell Reports

Molecular Architecture of Transcription Factor Hotspots in Early Adipogenesis

(2014) Rasmus Siersbæk et al.   Cell Reports

Analysis of Candida albicans Mutants Defective in the Cdk8 Module of Mediator Reveal Links between Metabolism and Biofilm Formation

(2014) Allia K. Lindsay et al.   PLoS Genetics

Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes

(2013) Warren A. Whyte et al.   CELL

Super-Enhancers in the Control of Cell Identity and Disease

(2013) Denes Hnisz et al.   CELL

Architectural Protein Subclasses Shape 3D Organization of Genomes during Lineage Commitment

(2013) Jennifer E. Phillips-Cremins et al.   CELL

HIF1A Employs CDK8-Mediator to Stimulate RNAPII Elongation in Response to Hypoxia

(2013) Matthew D. Galbraith et al.   CELL

The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator

(2013) M. A. Davis et al.   GENES & DEVELOPMENT

CDK8 Kinase Phosphorylates Transcription Factor STAT1 to Selectively Regulate the Interferon Response

(2013) Joanna Bancerek et al.   IMMUNITY

Activating RNAs associate with Mediator to enhance chromatin architecture and transcription

(2013) Fan Lai et al.   NATURE

A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction

(2013) Kuang-Lei Tsai et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants

(2013) S. C. J. Parker et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

CDK8 Maintains Tumor Dedifferentiation and Embryonic Stem Cell Pluripotency

(2012) A. S. Adler et al.   CANCER RESEARCH

MED12 Controls the Response to Multiple Cancer Drugs through Regulation of TGF-β Receptor Signaling

(2012) Sidong Huang et al.   CELL

A Sterol-Binding Protein Integrates Endosomal Lipid Metabolism with TOR Signaling and Nitrogen Sensing

(2012) Carl J. Mousley et al.   CELL

A Cardiac MicroRNA Governs Systemic Energy Homeostasis by Regulation of MED13

(2012) Chad E. Grueter et al.   CELL

Regulation of lipogenesis by cyclin-dependent kinase 8–mediated control of SREBP-1

(2012) Xiaoping Zhao et al.   JOURNAL OF CLINICAL INVESTIGATION

mRNA Decapping Factors and the Exonuclease Xrn2 Function in Widespread Premature Termination of RNA Polymerase II Transcription

(2012) Kris Brannan et al.   MOLECULAR CELL

The super elongation complex (SEC) family in transcriptional control

(2012) Zhuojuan Luo et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II

(2012) Stéphane Larochelle et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Extensive chromatin remodelling and establishment of transcription factor ‘hotspots’ during early adipogenesis

(2011) Rasmus Siersbaek et al.   EMBO JOURNAL

The Structure of CDK8/CycC Implicates Specificity in the CDK/Cyclin Family and Reveals Interaction with a Deep Pocket Binder

(2011) E.V. Schneider et al.   JOURNAL OF MOLECULAR BIOLOGY

Med12 is essential for early mouse development and for canonical Wnt and Wnt/PCP signaling

(2010) P. P. Rocha et al.   DEVELOPMENT

Mediator and cohesin connect gene expression and chromatin architecture

(2010) Michael H. Kagey et al.   NATURE

CDK8 is a positive regulator of transcriptional elongation within the serum response network

(2010) Aaron J Donner et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Activator-Mediator binding regulates Mediator-cofactor interactions

(2010) C. C. Ebmeier et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Nuclear CDKs Drive Smad Transcriptional Activation and Turnover in BMP and TGF-β Pathways

(2009) Claudio Alarcón et al.   CELL

The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function

(2009) M. T. Knuesel et al.   GENES & DEVELOPMENT

Complexity in Transcription Control at the Activation Domain-Mediator Interface

(2009) M. A. Balamotis et al.   Science Signaling

The Human CDK8 Subcomplex Is a Histone Kinase That Requires Med12 for Activity and Can Function Independently of Mediator

(2008) M. T. Knuesel et al.   MOLECULAR AND CELLULAR BIOLOGY

CDK8 is a colorectal cancer oncogene that regulates β-catenin activity

(2008) Ron Firestein et al.   NATURE