Affinage

TAF10

Transcription initiation factor TFIID subunit 10 · UniProt Q12962

Length
218 aa
Mass
21.7 kDa
Annotated
2026-04-28
20 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAF10 is a histone-fold domain subunit shared by the TFIID and SAGA transcriptional co-activator complexes, serving as an essential scaffold for complex integrity and a direct contact point between the general transcription machinery and gene-specific activators. TAF10 assembles with TAF8 and TAF2 into a cytoplasmic heterotrimer that is a precursor to nuclear holo-TFIID; because TAF10 lacks an intrinsic NLS, it depends on histone-fold partners TAF8, TAF3, or SPT7L for nuclear import (PMID:15870280, PMID:25586196). Loss of TAF10 destabilizes TFIID, arrests cell cycle progression, and blocks differentiation in a context-dependent manner—being essential in embryonic inner cell mass and fetal keratinocytes but dispensable in adult epidermis and presomitic mesoderm cyclic transcription (PMID:12773572, PMID:16039642, PMID:28893950). TAF10 activity is tuned by SET9-mediated monomethylation of a histone-fold lysine, which increases RNA Pol II affinity and potentiates transcription at specific promoters, and by LOXL2-catalyzed oxidation of that methylated lysine, which triggers TAF10 release from promoters to repress TFIID-dependent transcription of pluripotency genes (PMID:15099517, PMID:25959397).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1994 High

    Establishing that TAF10 functions as a gene-specific bridge within TFIID resolved how a general transcription factor could selectively mediate activation by specific regulators such as estrogen receptor AF-2.

    Evidence Co-immunoprecipitation of distinct TFIID populations and antibody-inhibition of in vitro transcription in human cell-free systems

    PMID:7923369

    Open questions at the time
    • No structural basis for the TAF10–ER interaction
    • Whether TAF10 contacts other activators was untested
  2. 1999 High

    Demonstrating that TAF10 loss causes G1 arrest, Rb hypophosphorylation, and apoptosis established that TAF10 is essential for cell viability and cell cycle progression, not merely modulatory.

    Evidence Cre-loxP knockout in murine F9 embryonal carcinoma cells with cell cycle analysis and rescue by human TAF10

    PMID:10469660

    Open questions at the time
    • Whether the phenotype reflects TFIID destabilization or loss of a TAF10-specific function was unclear
    • Genome-wide transcriptional impact not measured
  3. 2003 High

    Showing that TAF10 deletion collapses TFIID integrity and abolishes transcription in mouse embryo cells resolved whether TAF10 is a peripheral modulator or an essential structural subunit of holo-TFIID.

    Evidence Conditional knockout in mouse embryo cells with biochemical fractionation of TFIID and transcriptional run-on assays

    PMID:12773572

    Open questions at the time
    • Mechanism by which TAF10 stabilizes the full TFIID complex was unknown
    • Relative contribution of SAGA loss versus TFIID loss to phenotype was unresolved
  4. 2004 High

    Discovery that SET9 monomethylates TAF10 at a histone-fold lysine and that this increases RNA Pol II affinity revealed the first post-translational modification directly tuning a TAF's function within the preinitiation complex.

    Evidence In vitro methylation assay, affinity binding of methylated TAF10 to Pol II, reporter rescue in TAF10-null F9 cells with methylation-deficient mutant, ChIP for SET9

    PMID:15099517

    Open questions at the time
    • Identity of the specific lysine residue number was not universally mapped across species
    • Whether other methyltransferases contribute was untested
  5. 2005 High

    Revealing that TAF10 lacks an intrinsic NLS and piggybacks on histone-fold partners for nuclear import answered how an essential transcription factor reaches the nucleus and implied cytoplasmic pre-assembly as a regulatory step.

    Evidence Fluorescent fusion localization, NLS mutagenesis, importin-β binding assays, FRAP in living cells

    PMID:15870280

    Open questions at the time
    • How the choice among TAF8, TAF3, and SPT7L import routes is regulated was unknown
    • Whether cytoplasmic retention serves a regulatory function was untested
  6. 2005 High

    Context-dependent requirement of TAF10 was established by showing it is essential for fetal but not adult keratinocyte gene expression, revealing that TFIID/SAGA dependence varies with developmental state.

    Evidence Conditional Cre-loxP deletion in mouse keratinocytes, skin barrier assay, gene expression analysis

    PMID:16039642

    Open questions at the time
    • Which alternative transcriptional machinery compensates in adult epidermis was unknown
    • Whether TAF10-independent transcription uses TBP-free or partial TFIID complexes was unresolved
  7. 2015 High

    Crystal structure of the TAF8–TAF10 histone-fold pair and reconstitution of the cytoplasmic TAF2–TAF8–TAF10 heterotrimer defined the molecular pathway of TFIID subcomplex assembly before nuclear import.

    Evidence X-ray crystallography, native mass spectrometry, co-immunoprecipitation, biochemical reconstitution

    PMID:25586196

    Open questions at the time
    • How the heterotrimer is handed off to core-TFIID in the nucleus was not visualized
    • Kinetics of cytoplasmic assembly in vivo were unmeasured
  8. 2015 High

    Identification of LOXL2-mediated oxidation of methylated TAF10 as a mechanism to evict TAF10 from promoters established a two-step epigenetic switch—methylation then oxidation—controlling TFIID occupancy at pluripotency genes.

    Evidence Unbiased proteomic substrate identification, ChIP showing TAF10 promoter release, ES cell assays, zebrafish LOXL2 loss-of-function

    PMID:25959397

    Open questions at the time
    • Whether oxidized TAF10 is degraded or recycled was unknown
    • Genome-wide map of LOXL2-sensitive versus LOXL2-insensitive TAF10 targets was not generated
  9. 2015 High

    Direct interaction between TAF10 and GATA1 and the block in erythroid differentiation upon TAF10 ablation extended the activator-bridging paradigm beyond ER to a hematopoietic lineage-determining factor.

    Evidence Co-immunoprecipitation, mass spectrometry, ChIP, conditional erythroid-specific Cre-loxP deletion

    PMID:25870109

    Open questions at the time
    • Structural basis of TAF10–GATA1 interaction was undefined
    • Whether TAF10 contacts other hematopoietic transcription factors was untested
  10. 2017 High

    Demonstrating that TAF10-containing TFIID and SAGA are dispensable for cyclic gene transcription in presomitic mesoderm but required for lateral plate differentiation sharpened the model of tissue- and program-specific TFIID dependence.

    Evidence Conditional deletion in presomitic mesoderm, RNA-seq, complex integrity analysis in mouse embryos

    PMID:28893950

    Open questions at the time
    • Identity of the TAF10-independent transcriptional machinery supporting cyclic genes was not determined
    • Whether partial TFIID or TBP-free complexes substitute remains unresolved
  11. 2023 Medium

    Identifying TRIP12 as the E3 ubiquitin ligase that degrades TAF10 revealed a proteolytic axis linking TFIID subunit turnover to MYC protein levels and tumor growth control.

    Evidence CRISPR/Cas9 knockout, Western blot, cell culture assays, mouse xenograft model

    PMID:36639831

    Open questions at the time
    • Ubiquitination sites on TAF10 were not mapped
    • Whether TAF10 degradation is the sole mediator of MYC reduction was not fully dissected
    • Not independently confirmed by a second lab
  12. 2024 Medium

    Showing that METTL14-mediated m6A methylation of TAF10 mRNA reduces its stability added an epitranscriptomic layer of TAF10 regulation upstream of its protein-level modifications.

    Evidence MeRIP, RNA immunoprecipitation, luciferase mRNA stability reporter, Western blot, xenograft model

    PMID:38882361

    Open questions at the time
    • Specific m6A sites on TAF10 mRNA were not mapped at nucleotide resolution
    • Reader protein(s) mediating the stability effect were not identified
    • Single-lab finding not independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural model integrating SET9 methylation, LOXL2 oxidation, TRIP12 ubiquitination, and m6A-mediated mRNA control of TAF10 into a coherent regulatory circuit governing TFIID occupancy at specific promoters remains to be established.
  • No integrative study has addressed how the multiple TAF10 modifications are temporally coordinated
  • Genome-wide identification of TAF10-dependent versus TAF10-independent promoters in a single system is lacking
  • Structural basis for activator selectivity (ER vs GATA1 vs others) through TAF10 is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 4 R-HSA-1640170 Cell Cycle 1
Partners
GATA1LOXL2SET9SPT7LTAF2TAF3TAF8TRIP12
Complex memberships
SAGA/TFTCTAF2-TAF8-TAF10 heterotrimerTFIID

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Human TAF10 (hTAFII30) is a component of a distinct subset of TFIID complexes and directly interacts with the AF-2-containing region E of the estrogen receptor (ER), mediating transcriptional activation by ER AF-2 but not VP16 or ER AF-1. An antibody against hTAFII30 selectively inhibited ER AF-2-mediated transcription without affecting basal or VP16-activated transcription, demonstrating functionally distinct TFIID populations. Co-immunoprecipitation, antibody inhibition of transcription in cell-free systems, separation of distinct TFIID complexes Cell High 7923369
1997 TAF10 (TAFII30) stimulates transcription initiation ~20-fold in the presence of HMG-1 from an ERE-containing template in vitro, acting downstream of HMG-1-promoted ER-ERE binding, without itself affecting ER-ERE binding. In vitro transcription assay, EMSA with purified recombinant proteins Molecular endocrinology Medium 9212049
1999 TAF10 (TAFII30) is required for cell cycle progression in murine F9 embryonal carcinoma cells; TAF10-null cells arrest in G1/G0, show impaired cyclin E expression, hypophosphorylated Rb, and undergo apoptosis. TAF10 is required for parietal endodermal differentiation but not primitive endodermal differentiation induced by retinoic acid. Homologous recombination gene targeting, Cre-loxP deletion, cell cycle analysis, Western blot, rescue with human TAF10 The EMBO journal High 10469660
2000 Drosophila TAF10 homologs (dTAFII16 and dTAFII24) are components of dTFIID complexes, associating with TBP and other dTAFIIs; dTAFII24, but not dTAFII16, also associates with the histone acetyltransferase dGCN5, providing the first evidence for a TAF-GCN5-HAT complex in Drosophila. Co-immunoprecipitation, biochemical fractionation Molecular and cellular biology Medium 10669741
2003 TAF10 is required for TFIID stability in vivo; TAF10-deficient mouse embryo cells express normal levels of TBP and other TAFs but contain only partially formed TFIID, are endocycle arrested, and have undetectable transcription levels. TAF10 loss is lethal in inner cell mass but not trophoblast cells. Cre-loxP conditional knockout in mice, biochemical analysis of TFIID integrity, transcriptional run-on assay Molecular and cellular biology High 12773572
2004 SET9 methyltransferase 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, pointing to a direct role in preinitiation complex formation. This modification potentiates transcription of a subset of TAF10-dependent genes in a promoter-specific manner correlated with SET9 recruitment. In vitro methylation assay, affinity binding assay (methylated vs. unmethylated TAF10 binding to RNA Pol II), reporter assays in TAF10-null F9 cells with methylation-deficient TAF10 mutant, ChIP Molecular cell High 15099517
2005 TAF10 lacks an intrinsic nuclear localization signal (NLS) and depends on its histone-fold domain interaction partners (TAF8, TAF3, or SPT7L) for nuclear import. TAF8 and SPT7L carry NLS sequences that transport TAF10 to the nucleus; mutation of these NLS sequences retains TAF10 in the cytoplasm. TAF10 binds importin-beta in vitro only when co-expressed with TAF8 or TAF3 but not SPT7L. Once in the nucleus, FRAP shows TAF10 binds stably to nuclear structures. Fluorescent fusion protein localization, leptomycin B treatment, NLS mutagenesis, in vitro importin-beta binding assay, FRAP Molecular and cellular biology High 15870280
2005 TAF10 ablation in keratinocytes of the developing foetal epidermis impairs keratinocyte terminal differentiation and skin permeability barrier function by affecting expression of a subset of genes, but loss of TAF10 in adult epidermis has no detectable effect on gene expression or epidermal homeostasis, demonstrating developmental stage-specific requirement. Conditional Cre-loxP deletion in keratinocytes, skin barrier assay, gene expression analysis Developmental biology High 16039642
2007 TAF10 (TAFII30) mediates estrogen/ER-dependent repression of gene promoters by facilitating direct association of ER with core promoter sequences in a co-repressor complex containing SMRT and/or NCoR; this requires the E/F and DNA-binding domains of ER. Tamoxifen disrupts the ER-co-repressor complex at the promoter. TAFII30 is required for optimal core promoter activity and for the repressive association of ER. Biotinylated DNA pulldown from nuclear extracts, ChIP, siRNA knockdown, promoter-reporter assays, protein synthesis inhibition experiments Oncogene Medium 17599049
2015 TAF10 assembles with TAF2 and TAF8 into a heterotrimeric cytoplasmic subcomplex that is a precursor to nuclear holo-TFIID. TAF8 nucleates the complex; the TAF8-TAF10 histone fold domains adopt a non-canonical arrangement revealed by X-ray crystallography; TAF2 binds to multiple C-terminal motifs of TAF8, and these interactions dictate TAF2 incorporation into a nuclear core-TFIID complex. Native mass spectrometry, X-ray crystallography, co-immunoprecipitation, biochemical reconstitution, cellular fractionation Nature communications High 25586196
2015 LOXL2 enzymatically oxidizes methylated TAF10 (converting ε-amino groups of lysine to aldehyde groups), identified by unbiased proteomics. LOXL2-mediated oxidation of TAF10 induces its release from target promoters, blocking TFIID-dependent gene transcription and inactivating pluripotency genes in embryonic stem cells. Absence of LOXL2 in zebrafish results in aberrant Sox2 overexpression and impaired neural differentiation. Unbiased proteomic identification of LOXL2 substrates, ChIP showing TAF10 promoter release, ES cell pluripotency assays, zebrafish loss-of-function Molecular cell High 25959397
2015 TAF10 directly interacts with the GATA1 transcription factor as shown by co-immunoprecipitation and mass spectrometry; TAF10 is enriched on the GATA1 locus in human fetal erythroid cells by ChIP. Erythroid-specific ablation of TAF10 causes a differentiation block with deregulated GATA1 target genes including Gata1 itself. Co-immunoprecipitation, mass spectrometry, ChIP, conditional Cre-loxP deletion in erythroid cells Molecular and cellular biology High 25870109
2017 TAF10 is required for assembly of both TFIID and SAGA complexes in the mouse embryo; conditional Taf10 deletion in presomitic mesoderm (PSM) shows that TAF10-containing canonical TFIID and SAGA are dispensable for cyclic gene transcription and PSM segmental patterning but required for lateral plate differentiation, demonstrating context-dependent transcriptional roles. Conditional Cre-loxP deletion, RNA-seq, complex integrity analysis Development High 28893950
2017 Drosophila TAF10 and TAF10b (dTAFII16 and dTAFII24) share interaction partners and have partially redundant functions; dTAF10b loss causes pupal lethality while dTAF10 loss allows puparium formation but causes eye morphology defects. During DNA repair, dTAF10 and dTAF10b act redundantly. Double-mutant generation, transgenic rescue, in silico structural modeling, DNA repair assays Transcription Medium 28841365
2023 The E3 ligase TRIP12 induces TAF10 degradation via ubiquitination, which in turn reduces MYC protein levels; the small molecule Z363 activates TRIP12 to co-regulate both TAF10 and MYC, suppressing tumor growth. CRISPR/Cas9 KO, Western blot of TAF10/MYC levels, cell culture functional assays, mouse xenograft model Clinical and translational medicine Medium 36639831
2024 METTL14 promotes m6A methylation of TAF10 mRNA, suppressing TAF10 mRNA stability and reducing TAF10 protein levels; this was demonstrated by methylated RNA immunoprecipitation, RNA immunoprecipitation, and luciferase reporter assay for TAF10 mRNA stability. RNA immunoprecipitation, methylated RNA immunoprecipitation (MeRIP), luciferase reporter assay for mRNA stability, Western blot, xenograft mouse model Heliyon Medium 38882361

Source papers

Stage 0 corpus · 20 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 20 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
2006 Temporary expression of the TAF10 gene and its requirement for normal development of Arabidopsis thaliana. Plant & cell physiology 15 17148695
2005 Abundant expression in vascular tissue of plant TAF10, an orthologous gene for TATA box-binding protein-associated factor 10, in Flaveria trinervia and abnormal morphology of Arabidopsis thaliana transformants on its overexpression. Plant & cell physiology 13 15659449
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