Affinage

TAF5L

TAF5-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 5L · UniProt O75529

Length
589 aa
Mass
66.2 kDa
Annotated
2026-06-10
15 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAF5L is a non-enzymatic structural subunit of the SAGA (GNAT-HAT/PCAF) transcriptional coactivator complex that drives gene expression programs through histone H3K9 acetylation and transcription factor recruitment (PMID:31005419, PMID:42009663). Together with TADA1 and TAF6L, TAF5L forms the SAGA CORE module that maintains complex integrity and stabilizes the acetyltransferase KAT2A; loss of TAF5L disrupts SAGA, releasing chromatin-unbound KAT2A for proteasomal degradation via the E3 ligase UBR5 and deubiquitinase OTUD5, with consequent loss of H3K9ac (PMID:42009663). Cryo-EM of endogenous human SAGA shows that TAF5L and its partner TAF6L diverge structurally from their canonical TFIID paralogs (TAF5 and TAF6), and these rearrangements are required to accommodate the metazoan-specific splicing-factor (SPL) module within the complex (PMID:41849588). Functionally, SAGA-associated TAF5L activity sustains self-renewal of mouse embryonic stem cells by transcriptionally activating c-Myc and Oct4 networks through H3K9ac deposition and c-MYC recruitment (PMID:31005419), and is required in vivo for hematopoiesis, where its loss arrests immature hematopoietic cells in the bone marrow and upregulates interferon pathway genes (PMID:41577693, PMID:40475452).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2006 Medium

    Established that TAF5L can participate in core-promoter transcription complexes, providing the first evidence that it acts within variant TAF-containing assemblies rather than as a free factor.

    Evidence RT-PCR, in situ hybridization, and in vitro protein-DNA interaction assays in frog

    PMID:16412700

    Open questions at the time
    • Functional consequence on transcription inferred, not directly tested
    • Limited to frog ortholog and germ-cell expression context
    • No identification of the mammalian complex it acts within
  2. 2019 Medium

    Defined TAF5L as a coactivator that enhances a sequence-specific transcription factor, showing it boosts target gene expression without altering the factor's own mRNA level.

    Evidence Yeast two-hybrid, domain mapping, and siRNA knockdown with target readout in the clam Meretrix petechialis

    PMID:31743760

    Open questions at the time
    • Invertebrate model, single lab
    • Direct interaction shown by Y2H without orthogonal validation
    • Mechanism of transcriptional enhancement not resolved
  3. 2019 High

    Placed TAF5L within the GNAT-HAT/SAGA-PCAF coactivator complex and tied its function to a defined cellular program, resolving how it controls gene expression.

    Evidence Genome-wide CRISPR loss-of-function screen, H3K9ac ChIP-seq, RNA-seq, and molecular epistasis in mouse ESCs

    PMID:31005419

    Open questions at the time
    • Does not define TAF5L's structural role within SAGA
    • Mechanism linking TAF5L to KAT2A activity not yet shown
  4. 2025 High

    Demonstrated a non-redundant in vivo requirement for TAF5L in hematopoiesis, distinguishing its physiological role from the ESC self-renewal context.

    Evidence Genome-wide in vivo CRISPR knockout screen in HSPCs with bone marrow and transcriptomic profiling, plus a human MDS model

    PMID:40475452 PMID:41577693

    Open questions at the time
    • Causal link between SAGA disruption and the interferon/mitochondrial phenotypes not directly traced
    • Cell-intrinsic versus niche contributions not fully separated
  5. 2026 High

    Resolved the molecular basis of TAF5L's structural role: it is a CORE-module subunit whose integrity gates KAT2A protein stability via the ubiquitin-proteasome system.

    Evidence Fluorescence KAT2A stability reporter, CRISPR knockouts, proteomics, and a focused ubiquitin-proteasome CRISPR screen

    PMID:42009663

    Open questions at the time
    • Direct physical contacts between TAF5L and KAT2A not mapped
    • Whether UBR5/OTUD5 act on KAT2A directly versus indirectly not fully resolved
  6. 2026 High

    Provided the structural explanation for why metazoan TAF5L/TAF6L diverge from TFIID paralogs, showing the rearrangements are needed to dock the splicing-factor module.

    Evidence Cryo-EM of affinity-purified endogenous human SAGA complex

    PMID:41849588

    Open questions at the time
    • Functional consequence of SPL coupling for splicing or transcription not tested
    • TAF5L-specific contacts to SPL versus TAF6L-mediated docking not separated
  7. 2026 Medium

    Extended TAF5L function to adaptive immunity by showing it is sufficient to enhance suppressive CD8+ Treg identity, implicating it in immune-cell stability.

    Evidence Lentiviral TAF5L overexpression in primary human CD8+ Tregs with in vitro suppression assays and flow cytometry

    PMID:41630158

    Open questions at the time
    • Single overexpression approach, no loss-of-function confirmation
    • Pathway linking TAF5L to FOXP3 not dissected
    • Dependence on SAGA/KAT2A in this context untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TAF5L-dependent SAGA activity is selectively deployed across distinct cell types (ESC self-renewal, hematopoiesis, Treg function) and whether the SPL coupling links SAGA-driven transcription to splicing remains unresolved.
  • No mechanism for cell-type-specific gene selection by TAF5L/SAGA
  • Functional role of the SPL module not established
  • Direct TAF5L-KAT2A interaction interface unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-4839726 Chromatin organization 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
KAT2ATADA1TAF6L
Complex memberships
SAGA (GNAT-HAT/PCAF) coactivator complexSAGA CORE module

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 TAF5L and TAF6L are components/co-activators of GNAT-HAT (PCAF/SAGA) complexes in mouse ESCs and transcriptionally activate c-Myc and Oct4 and their corresponding MYC and CORE regulatory networks, primarily through H3K9ac deposition and c-MYC recruitment, thereby maintaining self-renewal. CRISPR-Cas9 loss-of-function screen, ChIP-seq (H3K9ac), RNA-seq, and molecular epistasis in mouse ESCs Molecular cell High 31005419
2026 TAF5L (together with TADA1 and TAF6L) is a non-enzymatic SAGA CORE module subunit required for KAT2A protein stability; loss of TAF5L disrupts SAGA complex integrity, releasing non-chromatin-bound KAT2A that is degraded by the proteasome (via E3 ligase UBR5 and deubiquitinase OTUD5), resulting in reduced H3K9 acetylation. Fluorescence-based KAT2A stability reporter, CRISPR knockouts, proteomic profiling, focused CRISPR screen of ubiquitin-proteasome system genes Nature communications High 42009663
2026 High-resolution cryo-EM structure of endogenous human SAGA reveals that TAF5L and TAF6L contain major structural differences from their canonical TFIID paralogs (TAF5 and TAF6); TAF6L HEAT repeat domain provides a docking surface for the metazoan-specific splicing-factor module (SPL), and these structural rearrangements in TAF5L/TAF6L are directly required to accommodate SPL within the SAGA complex. Cryo-EM structure of affinity-ligand-purified endogenous human SAGA complex Science advances High 41849588
2025 Loss of Taf5l in hematopoietic stem and progenitor cells strongly inhibits hematopoiesis in vivo, causing a buildup of immature hematopoietic cells in the bone marrow, associated with upregulation of interferon pathway genes, reduced mitochondrial activity, and increased megakaryocyte progenitor commitment; loss also enhances cell outgrowth and interferon pathway in a human MDS model. Genome-wide in vivo CRISPR knockout screen in HSPCs, bone marrow analysis, transcriptomic profiling Nature communications High 40475452 41577693
2006 TAF5L is preferentially expressed in testis and ovary during gametogenesis and embryogenesis in frogs; in vitro protein-DNA interaction assays demonstrated that TAF5L can participate in core promoter complexes as part of variant TAF-containing assemblies, consistent with a role in germ cell-specific transcription initiation. RT-PCR, in situ hybridization, in vitro protein-DNA interaction assays with recombinant proteins Gene expression patterns : GEP Medium 16412700
2019 In the clam Meretrix petechialis, MpTAF5L interacts with the transcription factor MpMITF (via the N-terminal TAF5-NTD2 domain of MpTAF5L) and enhances MpMITF transcriptional activation activity; knockdown of MpTAF5L decreased expression of the MITF target gene MpBcl-2 without changing MpMITF mRNA levels, indicating coactivator function. Yeast two-hybrid assay, domain mapping, siRNA knockdown with target gene expression analysis Fish & shellfish immunology Medium 31743760
2026 Lentiviral transduction of TAF5L in CD8+ Tregs boosted FOXP3 expression and was sufficient to enhance the suppressive function of these cells, identifying TAF5L as a molecular regulator of CD8+ Treg stability and function. Lentiviral transduction of TAF5L into primary human CD8+ Tregs, in vitro suppression assays, flow cytometry European journal of immunology Medium 41630158
2025 High-resolution cryo-EM structure of endogenous human SAGA (preprint version) shows that TAF5L and TAF6L structural differences from canonical TFIID paralogs are directly implicated in structural rearrangements required to accommodate the SPL splicing-factor module; SPL binds SAGA through a smaller interface than in U2snRNP, sharing a deeply inserted helical motif. Cryo-EM structure of affinity-ligand-purified endogenous human SAGA bioRxivpreprint Medium

Source papers

Stage 0 corpus · 15 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes. BMC medical genetics 38 18045485
2019 TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cells via the MYC Regulatory Network. Molecular cell 37 31005419
2006 Developmental and cell type-specific regulation of core promoter transcription factors in germ cells of frogs and mice. Gene expression patterns : GEP 37 16412700
2013 Complex multi-block analysis identifies new immunologic and genetic disease progression patterns associated with the residual β-cell function 1 year after diagnosis of type 1 diabetes. PloS one 19 23755131
2019 TAF5L functions as transcriptional coactivator of MITF involved in the immune response of the clam Meretrix petechialis. Fish & shellfish immunology 8 31743760
2021 Long non-coding RNAs and their targets as potential biomarkers in breast cancer. IET systems biology 7 33991433
2005 The TAF5L gene on chromosome 1q42 is associated with type 1 diabetes in Russian affected patients. Autoimmunity 6 16206511
2025 In vivo CRISPR screening identifies SAGA complex members as key regulators of hematopoiesis. bioRxiv : the preprint server for biology 4 40475452
2026 Stabilization of Human CD8+ Treg in Inflammatory Environments Through FOXP3 Expression. European journal of immunology 1 41630158
2026 Disruption of the SAGA CORE triggers collateral degradation of KAT2A. Nature communications 1 42009663
2025 Medications for opioid use disorder shape immune responses during chronic HIV infection. Cell reports. Medicine 1 40460829
2019 1q42.12q42.2 Deletion in a Child with Midline Defects and Hypoplasia of the Corpus Callosum. Molecular syndromology 1 31191205
2026 In vivo CRISPR screening identifies SAGA complex members as key regulators of hematopoiesis. Nature communications 0 41577693
2026 Genome-wide association study of nutrient composition in meat from three two-way crossbred pig populations using whole-genome resequencing. Frontiers in veterinary science 0 41696008
2026 Insights into the structure and evolution of the human SAGA complex by affinity-ligand purification. Science advances 0 41849588

Missed literature

Know a paper Affinage missed for TAF5L? Flag it for the maintainers and the community.

No submissions yet.