Affinage

TAF10

Transcription initiation factor TFIID subunit 10 · UniProt Q12962

Length
218 aa
Mass
21.7 kDa
Annotated
2026-06-10
18 papers in source corpus 16 papers cited in narrative 16 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

TAF10 is a histone-fold subunit shared by the TFIID and SAGA-type transcriptional co-activator complexes that supports RNA polymerase II transcription of defined gene subsets rather than all class II genes (PMID:7923369, PMID:10469660, PMID:12773572). It is essential for TFIID integrity: TAF10-null cells retain TBP and other TAFs but assemble only partial TFIID, lose detectable transcription, and arrest in the cell cycle, and loss is embryonic-lethal at the inner cell mass stage (PMID:10469660, PMID:12773572). TAF10 lacks an intrinsic nuclear localization signal and is imported only when bound to a histone-fold partner (TAF8, TAF3, or SPT7L); within the cytoplasm it joins TAF2 and TAF8 in a heterotrimeric submodule—assembled through a non-canonical TAF8–TAF10 histone-fold arrangement—that nucleates stepwise holo-TFIID assembly after nuclear import (PMID:15870280, PMID:25586196). Its activity is tuned by a methylation switch: SET9 monomethylates a loop-2 lysine in the histone-fold domain to raise affinity for RNA Pol II and potentiate transcription at SET9-targeted promoters, while LOXL2 oxidizes that same methylated lysine to release TAF10 from promoters and silence TFIID-dependent genes, including pluripotency factors in embryonic stem cells (PMID:15099517, PMID:25959397). TAF10 also confers promoter selectivity through direct contacts with sequence-specific factors—the estrogen receptor AF-2 domain, where it mediates both activation and ER-dependent core-promoter repression via SMRT/NCoR co-repressors, and GATA1, where it controls erythroid differentiation (PMID:7923369, PMID:17599049, PMID:25870109). Consistent with this gene-selective role, conditional ablation produces context-dependent developmental phenotypes in epidermis, erythroid cells, and mesoderm (PMID:16039642, PMID:25870109, PMID:28893950).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Established that TAF10 defines a functionally distinct subpopulation of TFIID and links the complex to a specific activator, answering whether all TFIID complexes are equivalent.

    Evidence Co-immunoprecipitation, biochemical fractionation of TFIID, and antibody inhibition of ER AF-2-mediated transcription

    PMID:7923369

    Open questions at the time
    • Did not define the structural basis of the TAF10-ER contact
    • Did not establish which genes depend on TAF10-containing TFIID in vivo
  2. 1997 Medium

    Placed TAF10 action at the transcription-initiation step rather than at DNA binding, clarifying its mechanistic position in ER-driven transcription.

    Evidence In vitro transcription and EMSA with purified recombinant TAF10, HMG-1, and ER

    PMID:9212049

    Open questions at the time
    • Reconstitution in a single lab with limited follow-up
    • Did not identify the contacts within the preinitiation complex through which TAF10 stimulates initiation
  3. 1999 High

    Showed that TAF10 is required for expression of only a subset of genes and for cell-cycle progression, distinguishing selective from general transcriptional roles.

    Evidence Cre-loxP knockout in F9 embryonal carcinoma cells with cyclin E and Rb phosphorylation readouts

    PMID:10469660

    Open questions at the time
    • Did not resolve whether the cell-cycle defect is direct or secondary to loss of specific target genes
    • Did not define the TAF10-dependent gene set
  4. 2003 High

    Demonstrated that TAF10 is structurally required for TFIID assembly in vivo and for early embryonic viability, explaining the molecular consequence of its loss.

    Evidence Conditional Cre-loxP knockout in mouse embryos with immunoblotting of TFIID components and transcription analysis

    PMID:12773572

    Open questions at the time
    • Did not define the order of assembly steps that fail without TAF10
    • Did not explain trophoblast versus inner cell mass differential survival
  5. 2004 High

    Identified a covalent regulatory switch by which SET9 methylation increases TAF10 affinity for RNA Pol II and potentiates transcription at specific promoters.

    Evidence In vitro methylation, RNA Pol II co-IP, site-directed mutagenesis, and reporter assays in TAF10-null cells

    PMID:15099517

    Open questions at the time
    • Did not define how SET9 is recruited to specific promoters
    • Did not establish the demethylation/reversal mechanism at the time
  6. 2005 High

    Resolved how a TAF10 lacking its own NLS reaches the nucleus, identifying histone-fold partner-dependent importin-beta-mediated import.

    Evidence Fluorescent fusion localization, NLS mutagenesis, FRAP, live imaging, and in vitro importin-beta binding

    PMID:15870280

    Open questions at the time
    • Did not establish which partner predominates in different cell types
    • Did not connect import regulation to gene-selective transcription
  7. 2007 Medium

    Extended TAF10's ER role to gene repression, showing it is required for repressive ER core-promoter association via SMRT/NCoR independent of ER-DNA binding.

    Evidence ChIP, biotin-promoter pulldown, siRNA knockdown, and reporter assays

    PMID:17599049

    Open questions at the time
    • Single lab
    • Did not determine generality of this repressive mechanism across ER target promoters
  8. 2015 High

    Defined the cytoplasmic TAF2-TAF8-TAF10 submodule and a non-canonical TAF8-TAF10 histone-fold interface, providing a stepwise model of holo-TFIID assembly.

    Evidence Native mass spectrometry, X-ray crystallography, co-IP, and biochemical reconstitution

    PMID:25586196

    Open questions at the time
    • Did not capture the full nuclear holo-TFIID assembly intermediates
    • Did not address how submodule formation is regulated in vivo
  9. 2015 High

    Completed the methylation switch by showing LOXL2 oxidizes methylated TAF10 to release it from promoters and silence TFIID-dependent and pluripotency genes.

    Evidence Proteomic substrate identification, ChIP, and functional assays in ES cells and zebrafish

    PMID:25959397

    Open questions at the time
    • Did not define how LOXL2 is targeted to specific TAF10-bound promoters
    • Did not establish reversibility of the oxidative modification
  10. 2015 High

    Linked TAF10 to a lineage-specific activator, showing direct GATA1 interaction and a requirement in erythroid differentiation.

    Evidence Conditional knockout, co-IP, ChIP, and mass spectrometry of TFIID/SAGA composition

    PMID:25870109

    Open questions at the time
    • Did not map the GATA1-TAF10 interaction interface
    • Did not separate TFIID- versus SAGA-mediated contributions
  11. 2017 Medium

    Defined the context-dependence of TAF10 requirement, showing TFIID/SAGA are dispensable in presomitic mesoderm but required for lateral plate differentiation.

    Evidence Conditional Cre-loxP knockout with transcriptome analysis and in situ hybridization in mouse mesoderm

    PMID:28893950

    Open questions at the time
    • Did not explain what substitutes for TFIID in PSM
    • Primarily a negative result with limited mechanistic placement
  12. 2017 Medium

    Characterized partial functional divergence and redundancy of Drosophila TAF10 paralogues, including redundancy in DNA repair.

    Evidence Genetic knockout, transgenic rescue, double-mutant analysis, and structural modeling in Drosophila

    PMID:28841365

    Open questions at the time
    • Limited molecular mechanistic detail
    • Relevance of the DNA-repair role to mammalian TAF10 unaddressed
  13. 2023 Low

    Implicated TAF10 turnover in oncogenic signaling, with TRIP12-induced degradation co-regulating TAF10 and MYC levels.

    Evidence CRISPR/Cas9 knockout, Western blot, and mouse xenograft model

    PMID:36639831

    Open questions at the time
    • Direct ubiquitination of TAF10 by TRIP12 not biochemically reconstituted
    • Single lab with limited mechanistic validation
  14. 2024 Medium

    Identified post-transcriptional control of TAF10 by METTL14-dependent m6A methylation reducing TAF10 mRNA stability in gastric cancer.

    Evidence RIP, MeRIP, luciferase reporter, Western blot, and xenograft model

    PMID:38882361

    Open questions at the time
    • Single lab
    • Did not establish the specific m6A reader mediating destabilization

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TAF10's methylation/oxidation switch, partner-dependent import, and activator contacts are integrated to select specific gene programs in a given cell type remains unresolved.
  • No unified model linking import, modification state, and promoter selectivity
  • Structure of full TAF10-containing holo-TFIID/SAGA on selective promoters not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ESR1GATA1LOXL2SET9SPT7LTAF2TAF3TAF8
Complex memberships
SAGA/TFTCTAF2-TAF8-TAF10 core submoduleTFIID

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 hTAFII30 (TAF10) is a component of a distinct subset of TFIID complexes and directly interacts with the AF-2-containing region E of the human estrogen receptor (ER), but not with ER AF-1 or VP16. An anti-hTAFII30 antibody inhibited ER AF-2-mediated transcriptional stimulation without affecting basal or VP16-activated transcription, demonstrating that functionally distinct TFIID populations exist that share common TAFIIs but differ in specific TAFIIs. Co-immunoprecipitation, antibody inhibition of transcription, biochemical fractionation of TFIID complexes Cell High 7923369
1997 Purified recombinant TAF(II)30 (TAF10) does not affect ER-ERE binding but stimulates transcription initiation ~20-fold in the presence of HMG-1, indicating TAF10 acts at the level of transcription initiation rather than DNA binding. HMG-1 promotes ER-ERE binding and TAF10 acts subsequently to stimulate transcription. In vitro transcription assay, electrophoretic mobility shift assay (EMSA) with purified recombinant proteins Molecular endocrinology Medium 9212049
1999 TAF(II)30 (TAF10) knockout in murine F9 embryonal carcinoma cells causes G1/G0 cell cycle arrest and apoptosis; cyclin E expression is impaired and retinoblastoma protein is hypophosphorylated in null cells. TAF10 is required for expression of a subset of genes but not for general class II gene transcription. Homologous recombination/Cre-loxP knockout, cell cycle analysis, Western blot for cyclin E and Rb phosphorylation The EMBO journal High 10469660
2000 Two Drosophila TAF10 homologues (dTAF(II)16 and dTAF(II)24) are both associated with TBP and other dTAF(II)s in dTFIID complexes; dTAF(II)24 (but not dTAF(II)16) is also associated with the histone acetyltransferase dGCN5, demonstrating that a TAF-GCN5-HAT complex exists in Drosophila. Co-immunoprecipitation, biochemical fractionation Molecular and cellular biology Medium 10669741
2003 TAF10 is required for TFIID stability in vivo: TAF10-null mouse embryo cells express normal TBP and other TAFs but contain only partially formed TFIID, are endocycle-arrested, and have undetectable transcription levels. TAF10 loss is lethal after blastocyst implantation (~E5.5), with inner cell mass but not trophoblast cells failing to survive. Conditional Cre-loxP knockout in mice, immunoblot for TFIID components, transcription analysis Molecular and cellular biology High 12773572
2004 SET9 monomethylates TAF10 at a single lysine residue in the loop 2 region of its histone-fold domain. Methylated TAF10 has increased affinity for RNA polymerase II. A methylation-deficient TAF10 mutant in TAF10-null F9 cells reveals that SET9-mediated methylation potentiates transcription of some but not all TAF10-dependent genes in a promoter-specific manner correlated with SET9 recruitment. In vitro methylation assay, co-immunoprecipitation with RNA Pol II, site-directed mutagenesis, reporter assays in TAF10-null cells Molecular cell High 15099517
2005 TAF10 lacks an intrinsic nuclear localization signal (NLS) and requires one of its three histone-fold domain-containing interaction partners (TAF3, TAF8, or SPT7L) for nuclear import. Mutation of NLS sequences in TAF8 or SPT7L retains TAF10 in the cytoplasm. TAF10 binding to importin-beta in vitro depends on co-expression of TAF8 or TAF3 (but not SPT7L). FRAP shows TAF10 does not associate with cytoplasmic partners but binds nuclear structures after import. Cytoplasmic-to-nuclear translocation of TAF10 occurs naturally during adult male germ cell differentiation. Fluorescent fusion protein localization, NLS mutagenesis, FRAP, in vitro importin-beta binding assay, live cell imaging Molecular and cellular biology High 15870280
2005 Conditional ablation of TAF10 in keratinocytes of the forming epidermis impairs keratinocyte terminal differentiation and alters skin permeability barrier functions and affects expression of some but not all genes. In contrast, loss of TAF10 in adult epidermis keratinocytes does not modify tested gene expression, affect epidermal homeostasis, or impair UV response or wound healing, demonstrating a developmental-stage-dependent requirement for TAF10. Conditional Cre-loxP knockout in mice, gene expression analysis, barrier function assays Developmental biology Medium 16039642
2007 TAFII30 (TAF10) is required for optimal core promoter activity and for the repressive association of estrogen receptor (ER) with the core promoter. E2 promotes ER association with the chromosomal P4 promoter in a TAFII30-dependent manner, forming a co-repressor complex with SMRT and/or NCoR; tamoxifen disrupts this complex. This mechanism mediates ER-dependent gene repression independently of direct ER-DNA binding. Chromatin immunoprecipitation (ChIP), biotin-promoter pulldown, siRNA knockdown, reporter assays Oncogene Medium 17599049
2015 TAF2, TAF8, and TAF10 form a heterotrimeric cytoplasmic subcomplex that is a precursor to nuclear holo-TFIID. TAF8 plays a central nucleating role. The TAF8-TAF10 interaction occurs through a non-canonical arrangement of their histone-fold domains. TAF2 binds to multiple motifs in the TAF8 C-terminal region, and this interaction dictates TAF2 incorporation into a core-TFIID complex in the nucleus, providing evidence for stepwise holo-TFIID assembly from preformed cytoplasmic submodules. Native mass spectrometry, X-ray crystallography, co-immunoprecipitation, biochemical reconstitution Nature communications High 25586196
2015 LOXL2 oxidizes methylated TAF10 (converting ε-amino groups to aldehyde groups on SET9-methylated lysine), causing TAF10 release from its target promoters and blocking TFIID-dependent gene transcription. In embryonic stem cells, this leads to inactivation of pluripotency genes. In zebrafish, loss of LOXL2 results in aberrant overexpression of the neural progenitor gene Sox2 and impaired neural differentiation. Unbiased proteomic/mass spectrometry identification of LOXL2 substrate, ChIP, functional assays in ES cells and zebrafish morpholino knockdown Molecular cell High 25959397
2015 TAF10 directly interacts with the GATA1 transcription factor and is enriched on the GATA1 locus in human fetal erythroid cells. Conditional ablation of TAF10 in erythroid cells causes a differentiation block accompanied by deregulation of GATA1 target genes including Gata1 itself, demonstrating functional cross-talk between TAF10 and GATA1 during erythropoiesis. Conditional Cre-loxP knockout in mice, co-immunoprecipitation (TAF10-GATA1 interaction), ChIP, mass spectrometry analysis of TFIID/SAGA complex composition Molecular and cellular biology High 25870109
2017 TAF10-containing TFIID and SAGA complexes are dispensable for early paraxial mesoderm (presomitic mesoderm) development: conditional deletion of Taf10 in PSM does not prevent cyclic gene transcription or PSM segmental patterning, and global mRNA levels are unchanged with only a minor gene subset dysregulated. However, lateral plate differentiation is profoundly altered by TAF10 loss. Conditional Cre-loxP knockout in mouse embryo mesoderm, transcriptome analysis, in situ hybridization Development Medium 28893950
2017 In Drosophila, dTAF10 and dTAF10b share interaction partners and show similar expression in neuronal tissues, but have partly distinct functions. Loss of dTAF10b causes pupal lethality while dTAF10 mutants form puparium but show distorted eye morphology. During DNA repair, dTAF10 and dTAF10b act redundantly. Genetic knockout, transgenic rescue experiments, double-mutant analysis, in silico structural modeling Transcription Medium 28841365
2023 The E3 ligase TRIP12 induces TAF10 degradation (in addition to directly ubiquitinating MYC), thereby reducing MYC protein levels indirectly. TAF10 and MYC are co-regulated by TRIP12, and the small molecule Z363 activates TRIP12 to suppress tumor growth through this dual mechanism. CRISPR/Cas9 knockout, Western blot, cell culture functional assays, mouse xenograft tumor model Clinical and translational medicine Low 36639831
2024 METTL14 promotes m6A methylation of TAF10 mRNA, suppressing TAF10 mRNA stability and reducing TAF10 protein levels. This post-transcriptional regulation negatively correlates with TAF10 expression and counteracts TAF10-dependent promotion of gastric cancer cell proliferation, migration, and invasion. RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP), luciferase reporter assay, Western blot, xenograft tumor model Heliyon Medium 38882361

Source papers

Stage 0 corpus · 18 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell 356 7923369
2004 Gene-specific modulation of TAF10 function by SET9-mediated methylation. Molecular cell 223 15099517
1999 Mammalian TAF(II)30 is required for cell cycle progression and specific cellular differentiation programmes. The EMBO journal 82 10469660
2015 Cytoplasmic TAF2-TAF8-TAF10 complex provides evidence for nuclear holo-TFIID assembly from preformed submodules. Nature communications 80 25586196
1997 High-mobility group (HMG) protein HMG-1 and TATA-binding protein-associated factor TAF(II)30 affect estrogen receptor-mediated transcriptional activation. Molecular endocrinology (Baltimore, Md.) 66 9212049
2003 TAF10 (TAF(II)30) is necessary for TFIID stability and early embryogenesis in mice. Molecular and cellular biology 56 12773572
2000 Two novel Drosophila TAF(II)s have homology with human TAF(II)30 and are differentially regulated during development. Molecular and cellular biology 52 10669741
2005 The nuclear import of TAF10 is regulated by one of its three histone fold domain-containing interaction partners. Molecular and cellular biology 45 15870280
2005 TAF10 is required for the establishment of skin barrier function in foetal, but not in adult mouse epidermis. Developmental biology 45 16039642
2015 LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation. Molecular cell 42 25959397
2015 TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis. Molecular and cellular biology 21 25870109
2007 Estrogen-induced and TAFII30-mediated gene repression by direct recruitment of the estrogen receptor and co-repressors to the core promoter and its reversal by tamoxifen. Oncogene 19 17599049
2017 The TAF10-containing TFIID and SAGA transcriptional complexes are dispensable for early somitogenesis in the mouse embryo. Development (Cambridge, England) 16 28893950
1995 Organization and chromosomal localization of the gene (TAF2H) encoding the human TBP-associated factor II 30 (TAFII30). Genomics 11 8530084
2024 METTL14 inhibits the malignant processes of gastric cancer cells by promoting N6-methyladenosine (m6A) methylation of TAF10. Heliyon 9 38882361
2023 Small molecule Z363 co-regulates TAF10 and MYC via the E3 ligase TRIP12 to suppress tumour growth. Clinical and translational medicine 8 36639831
2020 Deletions of the Idh1, Eco1, Rom2, and Taf10 Genes Differently Control the Hyphal Growth, Drug Tolerance, and Virulence of Candida albicans. Folia biologica 3 33069188
2017 TAF10 and TAF10b partially redundant roles during Drosophila melanogaster morphogenesis. Transcription 2 28841365

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