Affinage

MED7

Mediator of RNA polymerase II transcription subunit 7 · UniProt O43513

Length
233 aa
Mass
27.2 kDa
Annotated
2026-06-10
31 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MED7 is a conserved central scaffold subunit of the Mediator coactivator complex, required for activator-dependent RNA polymerase II transcription from yeast to human (PMID:9989412, PMID:9420330). Within the Mediator middle module it serves as a central binding platform, forming the structurally critical MED7·MED21 heterodimer—an extended fold built around a four-helix bundle and coiled-coil connected by a flexible hinge—and additional subcomplexes with Med31 (Med7C/31) and Med4/9, while also engaging Med10 and MED1 (PMID:15710619, PMID:19057509, PMID:20123732). The integrity of the MED7·MED21 hinge is essential for Mediator to bind RNA polymerase II and assemble the holoenzyme: point mutations leave core Mediator intact but disorder the middle module and abolish Pol II affinity (PMID:27821593). Mediator containing MED7 binds the Pol II C-terminal domain and stimulates its phosphorylation by TFIIH, coactivates enhancer-binding factors such as Sp1, and provides a direct binding site for MED1 whose ERK-phosphorylation-enhanced association with MED7 promotes nuclear receptor coactivation (PMID:9989412, PMID:9671713, PMID:18391015). Beyond initiation, MED7 regulates Pol II elongation through coding regions (PMID:22377631) and modulates subtelomeric chromatin silencing via Mediator occupancy and H4K16 acetylation balance (PMID:21482672). The human protein is constitutively SUMOylated (PMID:17709345), is required for Tat-dependent HIV-1 transcription at the TAR element (PMID:25100719), and its developmental and growth roles are conserved in C. elegans and Candida albicans (PMID:11728440, PMID:25375174).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1998 High

    Establishing that a Med7-containing Mediator complex physically engages the Pol II CTD and stimulates its phosphorylation defined Mediator's mechanistic link between activators and the basal transcription machinery.

    Evidence Biochemical purification of yeast and mammalian Mediator with CTD-binding and TFIIH phosphorylation assays in reconstituted in vitro transcription systems

    PMID:9420330 PMID:9671713

    Open questions at the time
    • Did not resolve which specific subunits contact the CTD
    • Med7's individual contribution within the complex not isolated
  2. 1999 High

    Identifying CRSP33/MED7 as a CRSP coactivator subunit whose depletion abolishes Sp1-dependent transcription placed MED7 directly in the pathway of enhancer-binding activator function.

    Evidence Biochemical purification, cloning, immunodepletion, and in vitro transcription with Sp1 in human cells

    PMID:9989412

    Open questions at the time
    • Did not define the molecular role of MED7 specifically versus other CRSP subunits
    • No structural basis for activator coactivation
  3. 2005 High

    The MED7·MED21 crystal structure revealed an extended four-helix-bundle architecture with a flexible hinge, providing a structural hypothesis for Mediator conformational change upon Pol II or activator binding.

    Evidence 3.0 Å X-ray crystallography of the MED7·MED21 heterodimer with functional surface analysis

    PMID:15710619

    Open questions at the time
    • Hinge function inferred structurally, not yet tested by mutation
    • Did not place the heterodimer in the assembled module
  4. 2007 Medium

    Confirming a direct, genetically supported MED7–MED21 interaction and discovering constitutive MED7 SUMOylation extended its characterization to subunit contacts and post-translational modification.

    Evidence High-copy suppression, reciprocal Co-IP in insect and bacterial systems, and UFDS-based SUMOylation screening with independent validation

    PMID:16758199 PMID:17709345

    Open questions at the time
    • Functional consequence of MED7 SUMOylation not determined
    • SUMO acceptor residue and regulation unresolved
  5. 2008 High

    Showing that ERK-phosphorylated MED1 binds directly to MED7 connected MAPK signaling to nuclear receptor coactivation through a defined subunit contact.

    Evidence Co-IP, in vitro binding, ERK phosphorylation assays, and in vitro transcription with thyroid hormone receptor

    PMID:18391015

    Open questions at the time
    • Phosphosite-to-MED7 interface not structurally mapped
    • In vivo dynamics of signal-regulated MED1 recruitment not shown
  6. 2010 High

    Reconstituting the recombinant middle module established MED7 as the central scaffold organizing three heterodimeric subcomplexes (Med7N/21, Med7C/31, Med4/9) at equimolar stoichiometry.

    Evidence Recombinant co-expression, native and ion-mobility MS, SAXS, and limited proteolysis of the yeast middle module

    PMID:20123732

    Open questions at the time
    • Atomic-resolution arrangement of the full module not resolved
    • Dynamics of subcomplex assembly not characterized
  7. 2011 Medium

    Linking Med7 to subtelomeric Mediator occupancy and the Sir2/Sas2 acetylation balance revealed a chromatin-level role beyond transcription initiation, affecting silencing and lifespan.

    Evidence ChIP of Mediator at telomeres, H4K16ac chromatin assays, expression analysis, and replicative lifespan measurement in yeast

    PMID:21482672

    Open questions at the time
    • Mechanism connecting Mediator occupancy to acetyltransferase balance unresolved
    • Conservation to human telomeres untested
  8. 2012 Medium

    Yeast ewe mutations showed Med7 controls Pol II transit through coding regions rather than promoter recruitment, establishing a post-initiation elongation function.

    Evidence Genetic analysis, Pol II ChIP at promoter and coding regions, 6-azauracil sensitivity, and reporter elongation assays

    PMID:22377631

    Open questions at the time
    • Molecular mechanism of elongation control not defined
    • Gene-specificity of the elongation role not mapped genome-wide
  9. 2014 Medium

    Knockdown and genome-wide profiling extended MED7 function to viral transcription and to organismal phenotypes, showing it is required for Tat-dependent HIV-1 transcription and for hyphal/biofilm programs and colonization in Candida.

    Evidence siRNA knockdown with HIV transcript and Tat reporter assays in human cells; conditional alleles, ChIP-chip and microarrays, and a mouse colonization model in C. albicans

    PMID:25100719 PMID:25375174

    Open questions at the time
    • Direct MED7 contact with the HIV TAR/Tat machinery not shown
    • Whether human MED7 occupies coding regions as in Candida untested
  10. 2016 High

    Targeted mutagenesis of the human MED21–MED7 hinge demonstrated that hinge integrity is required for Mediator–Pol II holoenzyme formation, converting the 2005 structural hypothesis into a tested mechanism.

    Evidence Affinity pull-down, subunit composition analysis, negative-stain EM of the Mediator–Pol II holoenzyme, and site-directed mutagenesis of hinge residues

    PMID:27821593

    Open questions at the time
    • Atomic detail of the hinge-Pol II contact not resolved
    • Effect on activator-dependent transcription in vivo not measured
  11. 2025 Medium

    Identifying E2F1-driven transcription of MED7 and its requirement for HCC cell proliferation and invasion implicated MED7 expression in a cancer phenotype.

    Evidence Dual-luciferase reporter, ChIP, siRNA knockdown, proliferation/migration/invasion assays, and xenograft model in hepatocellular carcinoma cells

    PMID:39935236

    Open questions at the time
    • Mediator-dependent transcriptional targets driving the phenotype not defined
    • Whether the effect reflects MED7's scaffolding role or a non-canonical activity unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MED7's distinct structural roles—holoenzyme assembly, elongation control, and chromatin silencing—are coordinated and regulated by modifications such as SUMOylation in human cells remains unresolved.
  • No integrated model linking SUMOylation to MED7 function
  • Human-cell mechanism of MED7 in elongation and silencing not established
  • Functional consequence of distinct subcomplex contacts in vivo unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 1
Partners
MED1MED10MED21MED31MED4MED6MED9
Complex memberships
CRSP coactivator complexMediator complexMediator middle moduleMediator–Pol II holoenzyme

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CRSP33 (MED7 homolog) is a subunit of the human CRSP coactivator complex (~700 kDa, nine subunits) required together with TAFIIs for transcriptional activation by Sp1; immunodepletion of CRSP subunits abolishes Sp1-dependent transcription. Biochemical purification, gene cloning, immunodepletion of CRSP from transcription reactions, in vitro transcription assay Nature High 9989412
1998 The mammalian (murine) Mediator complex contains a Med7 homolog that co-purifies with the complex; this complex binds to the RNA polymerase II C-terminal domain (CTD) and stimulates CTD phosphorylation by TFIIH. Biochemical purification, peptide sequencing, CTD-binding and TFIIH phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America High 9671713
1998 Yeast Med7 is a component of purified Mediator required for transcriptional activation in a fully defined in vitro system; the CTD of RNA polymerase II is required for Mediator function in vitro. Biochemical purification of yeast Mediator, in vitro transcription assay, CTD-requirement experiments Genes & development High 9420330
2005 The MED7·MED21 (Med7·Srb7) heterodimer forms a highly extended structure containing a four-helix bundle domain and a coiled-coil protrusion connected by a flexible hinge; this hinge is proposed to enable conformational changes in Mediator upon Pol II or activator binding. MED6 bridges via MED7·MED21 to the head module. X-ray crystallography (3.0 Å crystal structure of MED7·MED21 heterodimer), functional surface analysis The Journal of biological chemistry High 15710619
2008 MED1 directly binds to the MED7 subunit, and ERK (MAPK) phosphorylation of MED1 enhances this MED1–MED7 interaction, thereby promoting MED1 association with the Mediator complex and its nuclear receptor coactivator activity. Co-immunoprecipitation, in vitro binding assays, ERK phosphorylation assays, in vitro transcription with thyroid hormone receptor Molecular and cellular biology High 18391015
2008 The Med7N/31 submodule (N-terminal part of Med7 plus Med31/Soh1) adopts a novel fold in which two proline-rich stretches in Med7N wrap around the four-helix bundle of Med31; this submodule is required for activated transcription in vitro and has a predominantly positive function on expression of a specific gene subset (methionine metabolism, iron transport) in vivo. Crystal structure determination of Med7N/31, in vitro transcription assay with trans-complementation, in vivo transcriptome profiling, comparative phenotyping The EMBO journal High 19057509
2010 Within the recombinant yeast Mediator middle module (Med1, 4, 7, 9, 10, 21, 31), Med7 serves as a central binding platform forming three heterodimeric subcomplexes: Med7N/21, Med7C/31, and (with Med4) the Med4/9 pair; Med1 and Med10 also bind to Med7. Native mass spectrometry confirms equimolar stoichiometry of all seven subunits. Recombinant co-expression and purification, native mass spectrometry, ion-mobility MS, limited proteolysis, SAXS, protein-protein interaction assays Nucleic acids research High 20123732
2011 The Med7/Med21 four-helix bundle fold is a common building block shared with the head module Med11/22 heterodimer; this motif is predicted in several other Mediator heterodimers, indicating a multiplied and functionally diversified building block in Mediator evolution. Crystal structure of Med11/22, structural comparison with published Med7/Med21 structure, in vitro pre-initiation complex formation assay Nucleic acids research Medium 21498544
2013 A 3D model of the yeast Mediator middle module places the Med7/Med21 heterodimer at the center of a tetramer with Med4/Med9; Med10 and Med31 flank Med7/Med21. This elongated, flexible arrangement was determined by lysine–lysine cross-linking coupled to mass spectrometry. Chemical cross-linking mass spectrometry (XL-MS), arrangement of crystal structures and homology models into 3D model Nucleic acids research Medium 23939621
2007 CRSP9/MED7 (human) is constitutively SUMOylated in vivo, as identified by the Ubc9 fusion-dependent SUMOylation (UFDS) system, with SUMO modification confirmed independently of the fusion system. Ubc9 fusion-dependent SUMOylation (UFDS) screen, independent in vivo SUMOylation validation Nucleic acids research Medium 17709345
2016 The integrity of the conserved hinge region in the human MED21–MED7 heterodimer is required for Mediator binding to RNA polymerase II to form the holoenzyme; point mutations in the hinge leave core Mediator intact but increase disorder in the middle module and markedly reduce affinity for Pol II. Biochemistry (affinity pull-down, subunit composition analysis), negative-stain electron microscopy of Mediator–Pol II holoenzyme, site-directed mutagenesis of hinge residues The Journal of biological chemistry High 27821593
2012 Mutations in yeast Med7 (ewe alleles) located in or adjacent to the middle module severely diminish heat-shock-induced expression of HSP82 by impairing Pol II transit through the coding region rather than Pol II recruitment to the promoter, indicating a role for Med7 in regulating Pol II elongation. Genetic analysis (ewe mutations), ChIP of Pol II at promoter and coding regions, 6-azauracil sensitivity assay, reporter gene elongation assay Genetics Medium 22377631
2011 Mutations in yeast Med7 reduce Mediator occupancy at subtelomeric regions, causing a shift in Sir2/Sas2 balance and increased H4K16 acetylation near telomeres, leading to desilencing of subtelomeric genes and influencing cellular life span. ChIP of Mediator at telomeres, chromatin acetylation assays (H4K16ac), gene expression analysis, replicative lifespan measurement Molecular and cellular biology Medium 21482672
2007 In yeast, the genetic interaction between Med7 and Med21 (Srb7) is confirmed by high-copy suppression: overexpression of MED7 suppresses a temperature-sensitive med21 mutation. Co-immunoprecipitation of tagged proteins in insect cells and E. coli confirms a direct Med21–Med7 protein interaction dependent on residues 2–8 of Med21. High-copy suppressor screen, co-immunoprecipitation from insect cells and E. coli, two-hybrid assay Molecular genetics and genomics : MGG Medium 16758199
2001 C. elegans med-7 (let-49) is required for normal postembryonic development including gonad and germ cell development; RNAi knockdown demonstrates an additional role in embryogenesis. The gene was identified by molecular cloning and confirmed by rescue experiments. Genetic mapping and cloning of let-49/med-7 mutation, nonsense mutation identification, rescue experiments, RNAi knockdown FEBS letters Medium 11728440
2014 In Candida albicans, Med7 is non-essential for viability but is required for growth on specific carbon sources, hyphal formation, biofilm formation, and gastrointestinal colonization. Genome-wide ChIP shows Med7 occupies promoters of ~200 core genes under both yeast and hyphal conditions, with condition-specific expansion, and also occupies coding regions and 3′ ends. Loss of Med7 de-represses the ribosomal regulon. Conditional alleles, phenotypic assays, ChIP-chip genome-wide location profiling, gene expression microarrays, mouse colonization model PLoS genetics Medium 25375174
2007 In yeast, reducing the amount of Med7 (as well as Med/Nut2) suppresses the growth defect caused by NC2 depletion, indicating that Med7 (middle module) acts antagonistically to the NC2 repressor in basal transcription regulation. Genetic suppressor screen, genetic epistasis (NC2 depletion combined with med7 reduction) Genetics Low 17339209
2014 siRNA-mediated knockdown of MED7 in human cells significantly impairs HIV-1 replication at a post-integration step, specifically inhibiting transcription of nascent viral mRNA at the transactivation-responsive element (TAR) and impairing Tat-induced HIV transcription. siRNA knockdown, HIV replication assays, early/late HIV transcript quantification, Tat-dependent luciferase reporter assay The Journal of biological chemistry Medium 25100719
2025 E2F1 transcriptionally activates MED7 in hepatocellular carcinoma cells; knockdown of MED7 suppresses HCC cell proliferation, migration, invasion, and tube formation. Validated by dual-luciferase reporter assay and chromatin immunoprecipitation. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), siRNA knockdown, cell proliferation/migration/invasion assays, xenograft mouse model Chemical biology & drug design Medium 39935236

Source papers

Stage 0 corpus · 31 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1. Nature 296 9989412
1998 The Med proteins of yeast and their function through the RNA polymerase II carboxy-terminal domain. Genes & development 262 9420330
1998 Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways. Proceedings of the National Academy of Sciences of the United States of America 258 9671713
2008 Malleable machines in transcription regulation: the mediator complex. PLoS computational biology 104 19096501
2003 Quantitative analysis of binding of transcription factor complex to biotinylated DNA probe by a streptavidin-agarose pulldown assay. Analytical biochemistry 66 14622953
2005 A conserved mediator hinge revealed in the structure of the MED7.MED21 (Med7.Srb7) heterodimer. The Journal of biological chemistry 62 15710619
2008 MED1 phosphorylation promotes its association with mediator: implications for nuclear receptor signaling. Molecular and cellular biology 54 18391015
2008 Identification, structure, and functional requirement of the Mediator submodule Med7N/31. The EMBO journal 49 19057509
2007 A kinase subunit of the human mediator complex, CDK8, positively regulates transcriptional activation. Genes to cells : devoted to molecular & cellular mechanisms 40 17212659
2011 Mediator head subcomplex Med11/22 contains a common helix bundle building block with a specific function in transcription initiation complex stabilization. Nucleic acids research 38 21498544
2013 Model of the Mediator middle module based on protein cross-linking. Nucleic acids research 37 23939621
2010 Preparation and topology of the Mediator middle module. Nucleic acids research 36 20123732
2000 Purification and characterization of RNA polymerase II holoenzyme from Schizosaccharomyces pombe. The Journal of biological chemistry 35 10625684
2012 Role of Mediator in regulating Pol II elongation and nucleosome displacement in Saccharomyces cerevisiae. Genetics 33 22377631
2011 Mediator influences telomeric silencing and cellular life span. Molecular and cellular biology 30 21482672
2014 A functional portrait of Med7 and the mediator complex in Candida albicans. PLoS genetics 29 25375174
2014 Characterization of the influence of mediator complex in HIV-1 transcription. The Journal of biological chemistry 28 25100719
2009 Mutually exclusive STAT1 modifications identified by Ubc9/substrate dimerization-dependent SUMOylation. Nucleic acids research 28 19174562
2007 Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation. Nucleic acids research 28 17709345
2016 Role for the MED21-MED7 Hinge in Assembly of the Mediator-RNA Polymerase II Holoenzyme. The Journal of biological chemistry 24 27821593
2005 The Sp transcription factors are involved in the cellular expression of the human glucose-dependent insulinotropic polypeptide receptor gene and overexpressed in adrenals of patients with Cushing's syndrome. Journal of molecular endocrinology 23 16087722
2023 NLRs derepress MED10b- and MED7-mediated repression of jasmonate-dependent transcription to activate immunity. Proceedings of the National Academy of Sciences of the United States of America 21 37399403
2006 Functional and physical interactions within the middle domain of the yeast mediator. Molecular genetics and genomics : MGG 18 16758199
2012 Genome-wide profiling of pluripotent cells reveals a unique molecular signature of human embryonic germ cells. PloS one 17 22737227
2012 MC EMiNEM maps the interaction landscape of the Mediator. PLoS computational biology 13 22737066
2007 Specific defects in different transcription complexes compensate for the requirement of the negative cofactor 2 repressor in Saccharomyces cerevisiae. Genetics 11 17339209
2001 The MED-7 transcriptional mediator encoded by let-49 is required for gonad and germ cell development in Caenorhabditis elegans. FEBS letters 10 11728440
2017 ScMED7, a sugarcane mediator subunit gene, acts as a regulator of plant immunity and is responsive to diverse stress and hormone treatments. Molecular genetics and genomics : MGG 7 28785867
2021 Draft Genome Sequences and Genomic Analysis for Pigment Production in Bacteria Isolated from Blue Discolored Soymilk and Tofu. Journal of genomics 4 34646396
2023 Upregulation of MED7 was associated with progression in hepatocellular carcinoma. Cancer biomarkers : section A of Disease markers 3 38073375
2025 Baicalein Inhibits Tumor Property of Hepatocellular Carcinoma Cells Through the Inactivation of the E2F Transcription Factor 1/Mediator Complex Subunit 7 Axis. Chemical biology & drug design 1 39935236

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