Affinage

TAF13

Transcription initiation factor TFIID subunit 13 · UniProt Q15543

Length
124 aa
Mass
14.3 kDa
Annotated
2026-06-10
22 papers in source corpus 10 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAF13 (TAFII18) is a core histone-fold subunit of the general transcription factor TFIID that governs RNA polymerase II preinitiation complex (PIC) assembly across the genome (PMID:29111974, PMID:28918900). It pairs with TAF11 through reciprocal histone-fold domains to form a heterodimer, and this heterodimer engages the DNA-binding surface of TBP, competing with both TATA-box DNA and the TATA-mimicking N-terminal domain of TAF1; a conserved C-terminal TBP-interaction domain in TAF13 is required for cell growth (PMID:29111974). TAF13 is a bona fide TFIID component that provides functional contacts with TBP during PIC assembly, and its acute loss broadly reduces nascent transcription of nearly all Pol II genes regardless of TATA-box status or TAF1 enrichment (PMID:12840001, PMID:28918900). Genetically, TAF13/TFIID acts downstream of Mediator core-tail integrity in the transcriptional regulatory hierarchy (PMID:36331351). In mammals TAF13 is essential for development: its knockout blocks gastrulation and depletes the pluripotency factors OCT4, NANOG, and SOX2 in mouse embryos (PMID:38593904). Notably, loss of the TAF11-TAF13 heterodimer in mouse ESCs leaves overall TFIID integrity and TBP promoter recruitment largely intact yet still impairs PIC formation and globally reduces Pol II recruitment, revealing plasticity in PIC assembly pathways (PMID:40491483). Pathogenic missense variants in the TAF13 interface that forms the TAF11 heterodimer cause intellectual disability and microcephaly (PMID:28257693).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1996 Medium

    Established that the human TAFII18/TAF13 homologue is a genuine constituent of TFIID rather than an isolated factor, answering whether this small subunit belongs to the TBP-containing complex.

    Evidence Co-immunoprecipitation with TBP and the TAFII130 subunit in yeast plus essential-gene viability assay

    PMID:8962109

    Open questions at the time
    • Did not define how TAF13 contacts TBP
    • Membership demonstrated in yeast, not yet structurally resolved
  2. 1998 Medium

    Delimited the complex membership of TAFII18/TAF13 by showing it is excluded from the TBP-free STAGA complex, distinguishing it from related histone-fold subunits.

    Evidence Native complex immunoprecipitation and Western blotting from human cell extracts

    PMID:9726987

    Open questions at the time
    • Negative result from a single lab
    • Does not resolve TAF13's quantitative contribution to TFIID
  3. 1999 Medium

    Mapped the physical interface mediating the histone-fold heterodimer, showing specific alpha2-helix residues drive partner binding and synergistic activation with TBP.

    Evidence Mutagenesis of histone-fold residues and mammalian transcription assays with an altered-specificity TBP mutant

    PMID:10373554

    Open questions at the time
    • TAF13 inferred as binding partner rather than directly assayed
    • Single-lab in vivo transcription readout
  4. 2003 High

    Demonstrated that TAF11 and TAF13 provide functionally critical contacts with TBP during PIC assembly, linking the subunit to promoter recruitment in vivo.

    Evidence Temperature-sensitive yeast TAF mutants with genome-wide expression profiling and ChIP for PIC assembly

    PMID:12840001

    Open questions at the time
    • Temperature-sensitive alleles may produce indirect effects
    • Structural basis of TBP contact not defined
  5. 2017 High

    Resolved the structural logic of TAF13 function, showing the TAF11/TAF13 heterodimer binds the TBP DNA-binding surface in competition with TATA DNA and the TAF1 N-terminal domain, and defined a conserved CTID essential for growth.

    Evidence Crystal structure, cross-linking mass spectrometry, biochemical binding assays and mutagenesis

    PMID:29111974

    Open questions at the time
    • Functional consequence of TBP-surface competition for in vivo PIC dynamics not fully defined
    • Does not resolve order of events during PIC assembly
  6. 2017 High

    Connected TAF13 to human disease by showing missense variants that disrupt the TAF11-TAF13 heterodimer and TFIID incorporation cause intellectual disability and microcephaly.

    Evidence Co-immunoprecipitation with disease variants in HeLa cells, molecular modeling, and RNA-seq after TAF13 knockdown across two families

    PMID:28257693

    Open questions at the time
    • Causal chain from transcriptional deregulation to neurodevelopmental phenotype not established
    • E-box gene deregulation mechanism unresolved
  7. 2017 High

    Established that TAF13 is broadly required for TFIID-dependent transcription, showing acute depletion reduces nascent transcription of nearly all Pol II genes regardless of promoter class.

    Evidence Auxin-inducible degron depletion of yeast Taf13 with genome-wide nascent transcript measurement

    PMID:28918900

    Open questions at the time
    • Does not distinguish direct versus indirect effects on individual genes
    • Mechanism downstream of TBP contact not resolved
  8. 2022 Medium

    Positioned TAF13/TFIID downstream of Mediator core-tail integrity, ordering it within the transcriptional regulatory hierarchy.

    Evidence Genetic epistasis in yeast (Taf13 depletion x Med16 deletion) with mRNA expression profiling

    PMID:36331351

    Open questions at the time
    • Effect on TFIID genomic occupancy not fully resolved
    • Single-lab epistasis
  9. 2024 High

    Defined an essential mammalian developmental role, showing Taf13 is required for gastrulation and maintenance of the OCT4/NANOG/SOX2 pluripotency network.

    Evidence Mouse knockout with immunofluorescence for pluripotency markers and transcriptomic analysis

    PMID:38593904

    Open questions at the time
    • Whether pluripotency factor loss is a direct transcriptional effect not established
    • Stage-specific requirement before implantation untested
  10. 2025 High

    Revealed plasticity in PIC assembly, showing the TAF11-TAF13 heterodimer is dispensable for TBP/TFIID promoter recruitment yet still required for normal PIC formation and Pol II recruitment.

    Evidence Gene inactivation in mouse ESCs with ChIP-seq for TBP and Pol II, interpreted against cryo-EM models

    PMID:40491483

    Open questions at the time
    • Alternative PIC assembly pathway not molecularly defined
    • Reconciliation with broad transcriptional requirement seen in yeast incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TAF13's structural competition with TATA DNA and TAF1 is dynamically resolved during PIC assembly, and how this links to its developmental and disease functions, remains unresolved.
  • No time-resolved model of PIC assembly steps requiring TAF11/TAF13
  • Mechanism linking transcriptional defects to pluripotency loss and neurodevelopmental disease unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1266738 Developmental Biology 1 R-HSA-1643685 Disease 1
Partners
TAF1TAF11TBP
Complex memberships
TFIID

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 TAF11 and TAF13 form a ternary complex with TBP via their histone fold (HF) domains. TAF11/TAF13 competes with TATA-box DNA for binding to the DNA-binding surface of TBP, and also competes with the N-terminal domain of TAF1 (previously implicated in TATA-box mimicry). A highly conserved C-terminal TBP-interaction domain (CTID) in TAF13 is essential for supporting cell growth. Crystal structure determination, cross-linking mass spectrometry (CLMS), biochemical binding assays, mutagenesis eLife High 29111974
2017 Pathogenic missense variants in TAF13 (p.Met40Lys and p.Leu31His) impair formation of the TAF13-TAF11 histone-like heterodimer, which is required for recruitment of TAF11/TAF13 into TFIID. This disruption is associated with intellectual disability and microcephaly. TAF13 knockdown in neuroblastoma cells leads to deregulation of genes related to neuronal and skeletal functions and those containing E-box motifs. Co-immunoprecipitation in HeLa cells, molecular modeling, RNA sequencing upon TAF13 knockdown American journal of human genetics High 28257693
2003 In yeast TFIID, TAF11 and TAF13 provide critical functional contacts with TBP during preinitiation complex (PIC) assembly, as revealed by temperature-sensitive mutant analysis; loss of TAF13 function reduces TBP recruitment to promoters. Temperature-sensitive yeast mutants, genome-wide expression profiling, chromatin immunoprecipitation for PIC assembly The EMBO journal High 12840001
1999 Specific amino acids in the alpha2-helix of hTAFII28 (TAF13's heterodimer partner) mediate interaction with TAFII18 (TAF13) at the hydrophobic interface; mutation of these residues abolishes the hTAFII28-TAFII18 interaction and disrupts synergistic transcriptional activation with TBP. Mutagenesis of histone fold domain residues, mammalian cell transcription assays with altered-specificity TBP mutant Molecular and cellular biology Medium 10373554
1996 Yeast TAF19 (FUN81), the homologue of human TAFII18/TAF13, co-immunoprecipitates with TBP and is present in complexes containing the TAFII130 subunit, establishing it as a bona fide component of the TFIID complex. Coimmunoprecipitation, sequence homology, essential gene viability assay in yeast Proceedings of the National Academy of Sciences of the United States of America Medium 8962109
1998 Human TAFII18 (TAF13) is not associated in vivo with human TBP/TFIID or with a TFIID-related TBP-free TAF complex, establishing that it is not a component of the human STAGA complex (which contains the related hSPT3). Native complex immunoprecipitation and Western blotting from human cell extracts The Journal of biological chemistry Medium 9726987
2017 Rapid degron-dependent depletion of yeast Taf13 strongly reduces nascent transcription of nearly all RNA Pol II-transcribed genes, demonstrating that TAF13 is broadly required for TFIID-dependent transcription across gene classes (TATA and TATA-less, Taf1-enriched and Taf1-depleted). Auxin-inducible degron depletion, nascent transcription measurement (NET-seq/GRO-seq type assay), genome-wide Molecular cell High 28918900
2024 Taf13 knockout in mice causes embryonic lethality after implantation; Taf13-null embryos successfully implant and form egg-cylinder stages but fail to initiate gastrulation. TAF13 deficiency leads to depletion of pluripotency factors OCT4, NANOG, and SOX2, demonstrating an essential role in maintaining pluripotency. Conditional/constitutive mouse knockout, immunofluorescence for pluripotency markers, transcriptomic analysis Developmental biology High 38593904
2025 In mouse embryonic stem cells, Taf13 loss had little effect on overall TFIID integrity and caused only a mild reduction of TBP promoter recruitment, but led to altered PIC formation and globally reduced RNA Pol II recruitment. Thus, the TAF11-TAF13 heterodimer is not essential for TBP/TFIID promoter recruitment, revealing plasticity in PIC assembly pathways. Gene inactivation in mouse ESCs, ChIP-seq for TBP and Pol II, cryo-EM-informed genetic analysis iScience High 40491483
2022 In yeast, depletion of Taf13 suppresses the overactivation of TFIID-dependent genes caused by separation of Mediator core and tail modules, placing TAF13/TFIID downstream of Mediator core-tail integrity in the transcriptional regulatory hierarchy. Genetic epistasis in yeast (double mutant: Taf13 depletion × Med16 deletion), mRNA expression profiling G3 (Bethesda, Md.) Medium 36331351

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 A human SPT3-TAFII31-GCN5-L acetylase complex distinct from transcription factor IID. The Journal of biological chemistry 166 9726987
1996 Yeast RSP5 and its human homolog hRPF1 potentiate hormone-dependent activation of transcription by human progesterone and glucocorticoid receptors. Molecular and cellular biology 140 8649367
2017 Transcription of Nearly All Yeast RNA Polymerase II-Transcribed Genes Is Dependent on Transcription Factor TFIID. Molecular cell 129 28918900
2003 Systematic analysis of essential yeast TAFs in genome-wide transcription and preinitiation complex assembly. The EMBO journal 88 12840001
1996 Yeast homologues of higher eukaryotic TFIID subunits. Proceedings of the National Academy of Sciences of the United States of America 83 8962109
2006 ATM and ATR pathways signal alternative splicing of Drosophila TAF1 pre-mRNA in response to DNA damage. Molecular and cellular biology 61 17030624
2017 Architecture of TAF11/TAF13/TBP complex suggests novel regulation properties of general transcription factor TFIID. eLife 42 29111974
2017 Hypomorphic Pathogenic Variants in TAF13 Are Associated with Autosomal-Recessive Intellectual Disability and Microcephaly. American journal of human genetics 29 28257693
2020 TAF1 Transcripts and Neurofilament Light Chain as Biomarkers for X-linked Dystonia-Parkinsonism. Movement disorders : official journal of the Movement Disorder Society 25 32975318
1999 Synergistic transcriptional activation by TATA-binding protein and hTAFII28 requires specific amino acids of the hTAFII28 histone fold. Molecular and cellular biology 22 10373554
2007 A common cis-element in promoters of protein synthesis and cell cycle genes. Acta biochimica Polonica 17 17351670
1999 CD36 antisense expression in 3T3-F442A preadipocytes. Molecular and cellular biochemistry 16 10331653
2024 TATA-binding associated factors have distinct roles during early mammalian development. Developmental biology 9 38593904
2016 Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets. Proceedings of the National Academy of Sciences of the United States of America 6 26966232
2008 Involvement of GTA protein NC2beta in neuroblastoma pathogenesis suggests that it physiologically participates in the regulation of cell proliferation. Molecular cancer 6 18538002
2021 STAU2 binds a complex RNA cargo that changes temporally with production of diverse intermediate progenitor cells during mouse corticogenesis. Development (Cambridge, England) 5 34345913
2022 Involvement of the SAGA and TFIID coactivator complexes in transcriptional dysregulation caused by the separation of core and tail Mediator modules. G3 (Bethesda, Md.) 2 36331351
1999 Genomics of the human genes encoding four TAFII subunits of TFIID, the three subunits of TFIIA, as well as CDK8 and SURB7. Somatic cell and molecular genetics 2 11441538
2025 The transcription factor IID subunit Taf13 is dispensable for TATA binding protein promoter recruitment and RNA polymerase II transcription. iScience 1 40491483
2022 Identification of DNA Repair-Related Genes Predicting Clinical Outcome for Thyroid Cancer. Journal of oncology 1 35035484
2025 Two New Families With TAF13 Variant Presenting With Syndromic 46,XY Disorder of Sex Development: Expanding the Clinical Phenotype. American journal of medical genetics. Part A 0 40679298
2025 Machine learning-enabled identification of nucleus pulposus senescence-associated genes as potential biomarkers for intervertebral disc degeneration. European journal of medical research 0 41024137

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