Affinage

SGF29

SAGA-associated factor 29 · UniProt Q96ES7

Length
293 aa
Mass
33.2 kDa
Annotated
2026-06-10
10 papers in source corpus 9 papers cited in narrative 9 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SGF29 is a histone-mark reader subunit of the SAGA and ATAC histone acetyltransferase/co-activator complexes that couples recognition of active-promoter chromatin to GCN5-family histone acetylation (PMID:21685874, PMID:23894581). Its tandem Tudor domains pack face-to-face to form a dual-pocket cleft in which one pocket binds the H3 A1 residue and the other the methylated K4; the limited cleft length confers selectivity for H3K4me2/3, and this recognition is required for recruitment of SAGA to target loci and consequent histone H3 acetylation (PMID:21685874). Through this reader activity SGF29 maintains H3K4me3 and directs H3K14 acetylation at inducible promoters, coordinating with the SET1/MLL component ASH2L to sustain the H3K4me3 mark itself (PMID:23894581). As a complex component it interacts with ADA3, GCN5 and SPT3 and is recruited with c-Myc to activate c-Myc target genes, supporting transformation and metastasis (PMID:17334388). SGF29 supports distinct gene-expression programs across contexts: it sustains pluripotency by interacting with Oct4 and Nanog and maintaining H3K9 acetylation and chromatin accessibility at pluripotency genes in ESCs and pre-implantation embryos (PMID:41843375); during senescence it forms liquid-like nuclear condensates via Arg207 in its intrinsically disordered region, an activity that together with H3K4me3 binding is required to recruit transcription factors and co-activators and activate senescence genes including CDKN1A (PMID:37935676); and it is a nononcogenic dependency in acute myeloid leukemia, where its Tudor domain is required for transcription of oncogenes such as MEIS1 and for leukemogenesis (PMID:38048593).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2007 Medium

    Established SGF29 as a physical component of TFTC/STAGA co-activator complexes and linked it to oncogenic transcription, answering whether SGF29 is part of an acetyltransferase complex and has a functional output.

    Evidence Co-IP with ADA3/GCN5/SPT3, ChIP at c-Myc targets, siRNA knockdown with tumor xenograft assays in rat cells

    PMID:17334388

    Open questions at the time
    • Did not define the structural basis of SGF29's role in the complex
    • Direct molecular activity of SGF29 (mark reading) not yet established
  2. 2010 Medium

    Determined that the C-terminal tandem Tudor region adopts a discrete, crystallizable fold, setting up high-resolution structural analysis.

    Evidence Preliminary X-ray crystallography of yeast Sgf29 Tudor domain to 1.92 Å

    PMID:20693663

    Open questions at the time
    • No ligand-bound structure or functional assay in this report
    • Binding specificity unknown at this stage
  3. 2011 High

    Defined the molecular mechanism of SGF29 as an H3K4me2/3 reader via a dual-pocket tandem Tudor cleft and showed this recognition is required for SAGA recruitment and H3 acetylation, answering how SGF29 targets the complex to chromatin.

    Evidence Crystal structures of yeast and human SGF29 Tudor domains bound to H3K4me2/3 peptides, binding-pocket mutagenesis, in vivo ChIP and acetylation assays

    PMID:21685874

    Open questions at the time
    • Does not address SGF29 function outside SAGA recruitment
    • Cell-type and gene-program specificity not addressed
  4. 2013 Medium

    Showed SGF29 belongs to both SAGA and ATAC and coordinates H3K4me3 maintenance with H3K14 acetylation at inducible promoters, extending its reader role to crosstalk with SET1/MLL machinery.

    Evidence siRNA knockdown, ChIP for H3K4me3/H3K14ac and ASH2L, RT-PCR, mass spectrometry complex identification at ER stress genes

    PMID:23894581

    Open questions at the time
    • Mechanism by which SGF29 promotes ASH2L association unclear
    • Direct vs indirect effect on H3K4me3 deposition not resolved
  5. 2013 Medium

    Distinguished an acetyltransferase-independent boundary-forming function of Sgf29 in yeast, indicating SGF29 has roles separable from Gcn5 catalytic activity.

    Evidence Yeast genetic boundary assay with domain truncation and in vivo telomere boundary analysis

    PMID:24307402

    Open questions at the time
    • Molecular basis of boundary activity unknown
    • Relevance to human SGF29 not established
  6. 2023 Medium

    Revealed that SGF29 forms phase-separated nuclear condensates driven by Arg207 in its IDR, and that condensation acts together with H3K4me3 binding to drive senescence gene transcription, adding a biophysical layer to its co-activator function.

    Evidence R207 mutagenesis, live-cell phase-separation imaging, ChIP-seq, ATAC-seq, RNA-seq and co-activator recruitment in human progenitor cells and fibroblasts

    PMID:37935676

    Open questions at the time
    • Whether condensation operates outside senescence is unaddressed
    • Composition of the condensates not fully defined
  7. 2024 Medium

    Identified SGF29's Tudor reader function as a nononcogenic dependency required for AML oncogene transcription and leukemogenesis, nominating it as a therapeutic target.

    Evidence CRISPR-Cas9 domain-focused screen, CRISPR droplet sequencing, in vivo AML models

    PMID:38048593

    Open questions at the time
    • Direct Tudor-domain inhibitors not yet validated in this study
    • Mechanism linking SGF29 specifically to MEIS1 regulation not fully detailed
  8. 2024 Low

    Placed SGF29 functionally in telomere maintenance by promoting the Alternative Lengthening of Telomeres pathway.

    Evidence High-throughput imaging-based CRISPR screen (TAILS) with native FISH readout (preprint)

    PMID:bio_10.1101_2024.11.15.623791

    Open questions at the time
    • Single screening hit with no SGF29-specific mechanistic follow-up
    • Not yet peer-reviewed
    • Connection to its reader/co-activator function unexplored
  9. 2026 Medium

    Established a role for SGF29 in maintaining pluripotency through interaction with Oct4 and Nanog and control of H3K9 acetylation and chromatin accessibility, extending its function to developmental gene programs.

    Evidence mESC knockout/knockdown, Co-IP of Sgf29 with Oct4/Nanog, ChIP-seq for H3K9ac and TF binding, ATAC-seq, pre-implantation embryo assays

    PMID:41843375

    Open questions at the time
    • Whether Oct4/Nanog binding is direct or complex-mediated not resolved
    • Structural basis of TF interaction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SGF29's single reader/condensate biochemistry is redirected to produce context-specific gene programs (pluripotency vs senescence vs leukemia) and whether its acetyltransferase-independent and telomere-associated activities reflect a common mechanism.
  • No unifying model for context-specific target selection
  • ALT/telomere role lacks mechanistic confirmation
  • Direct Tudor-domain inhibitor pharmacology not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Complex memberships
ATACSAGATFTC/STAGA

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 Crystal structures of the tandem Tudor domains of S. cerevisiae and human SGF29 bound to H3K4me2 and H3K4me3 peptides revealed that the two Tudor domains pack face-to-face, with one pocket accommodating the H3A1 residue and the other the methylated K4 residue. The limited cleft length between the two pockets confers selectivity for H3K4me2/3. In vitro and in vivo functional assays demonstrated that H3K4me2/3 recognition by SGF29 is required for SAGA complex recruitment to target gene loci and consequent histone H3 acetylation. Crystal structure (X-ray crystallography), peptide binding assays, in vivo ChIP and histone acetylation assays, mutagenesis of binding pockets The EMBO journal High 21685874
2010 The tandem Tudor domain at the C-terminus of S. cerevisiae Sgf29 was successfully crystallized and diffracted to 1.92 Å resolution, confirming the domain adopts a distinct structural fold amenable to high-resolution analysis. X-ray crystallography (preliminary crystallographic analysis) Acta crystallographica. Section F, Structural biology and crystallization communications Medium 20693663
2007 Rat SGF29 directly interacted with rADA3 (direct interaction) and co-immunoprecipitated with rGCN5 and rSPT3, establishing it as a component of the TFTC/STAGA complexes. SGF29 was recruited to c-Myc target gene promoters together with c-Myc and activated c-Myc target gene expression. Knockdown of rSGF29 suppressed c-Myc target gene expression and inhibited anchorage-independent growth, tumorigenicity, and lung metastasis. Co-immunoprecipitation, ChIP, gene expression assays, siRNA knockdown, in vivo tumor xenograft assay Oncogene Medium 17334388
2013 Human SGF29 is a subunit of both the SAGA and ATAC histone acetyltransferase/co-activator complexes. SGF29 knockdown impaired transcription of ER stress genes GRP78 and CHOP, and reduced H3K14 acetylation at these loci. Additionally, SGF29 was required for maintenance of H3K4me3 at these promoters prior to ER stress; reduced H3K4me3 in SGF29-depleted cells correlated with decreased association of ASH2L (a core SET1/MLL complex component) at these gene loci, indicating a role for SGF29 in coordinating both H3K4me3 maintenance and H3K14 acetylation. siRNA knockdown, ChIP, quantitative RT-PCR, mass spectrometry-based complex identification PloS one Medium 23894581
2013 In S. cerevisiae, domain analysis identified two minimal boundary-forming regions in Sgf29: the N-terminal region (aa 1–12) and the Tudor domain-containing C-terminal region (aa 110–255). Critically, the boundary formation activity of these minimal regions was shown to be independent of Gcn5 acetyltransferase activity, and in vivo analysis showed Sgf29 and Gcn5 perform distinct functions at native telomere boundary regions. Yeast genetic boundary assay, domain deletion/truncation analysis, in vivo telomere boundary assay Journal of biochemistry Medium 24307402
2023 SGF29 forms liquid-like nuclear condensates during cellular senescence in human mesenchymal progenitor cells and fibroblasts via phase separation. Arg207 within the intrinsically disordered region is the key residue for condensate formation. Both condensate formation and H3K4me3 binding are required for SGF29 to establish its chromatin localization, recruit transcription factors and co-activators to specific genomic loci, and activate senescence-associated genes including CDKN1A. Condensate formation alone is not sufficient for H3K4me3 binding or transactivation. Mutagenesis (R207 mutation), live-cell imaging of phase separation, ChIP-seq, ATAC-seq, RNA-seq, co-activator recruitment assays Cell discovery Medium 37935676
2024 CRISPR-Cas9 domain-focused screen identified SGF29 as required for transcription of AML oncogenes including MEIS1. SGF29 deletion impaired leukemogenesis across multiple AML subtype models, establishing the SGF29 Tudor domain (H3K4me3 reader function) as a nononcogenic dependency in AML. CRISPR-Cas9 domain-focused library screen, CRISPR droplet sequencing, in vivo leukemia models Blood Medium 38048593
2026 In mouse ESCs, Sgf29 knockout reduced H3K9ac and chromatin accessibility at promoters and enhancers of pluripotency genes, triggering differentiation. Sgf29 was shown to interact with Oct4 and Nanog (but not Sox2) to co-regulate pluripotency gene expression. Sgf29 KO reduced Oct4 binding to Nanog and Klf4 loci. Sgf29 knockdown in pre-implantation embryos reduced blastocyst rate and decreased H3K9ac, with aberrant Oct4 and Nanog expression. Knockout/knockdown in mESCs, co-immunoprecipitation (Sgf29 with Oct4/Nanog), ChIP-seq for H3K9ac and transcription factor binding, ATAC-seq, pre-implantation embryo assays Science China. Life sciences Medium 41843375
2024 A high-throughput imaging-based CRISPR screen (TAILS) identified SGF29 as a promoter of the Alternative Lengthening of Telomeres (ALT) pathway, placing SGF29 functionally in telomere maintenance via recombination. High-throughput CRISPR screen with native FISH-based optical readout (TAILS) bioRxivpreprint Low bio_10.1101_2024.11.15.623791

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Sgf29 binds histone H3K4me2/3 and is required for SAGA complex recruitment and histone H3 acetylation. The EMBO journal 211 21685874
2013 A dual role for SAGA-associated factor 29 (SGF29) in ER stress survival by coordination of both histone H3 acetylation and histone H3 lysine-4 trimethylation. PloS one 39 23894581
2020 The Ada2/Ada3/Gcn5/Sgf29 histone acetyltransferase module. Biochimica et biophysica acta. Gene regulatory mechanisms 36 32890768
2023 SGF29 nuclear condensates reinforce cellular aging. Cell discovery 31 37935676
2007 Deregulated expression of a novel component of TFTC/STAGA histone acetyltransferase complexes, rat SGF29, in hepatocellular carcinoma: possible implication for the oncogenic potential of c-Myc. Oncogene 29 17334388
2024 Transcriptional control of leukemogenesis by the chromatin reader SGF29. Blood 14 38048593
2013 The N-terminus and Tudor domains of Sgf29 are important for its heterochromatin boundary formation function. Journal of biochemistry 12 24307402
2015 SGF29 and Sry pathway in hepatocarcinogenesis. World journal of biological chemistry 8 26322172
2010 Cloning, purification, crystallization and preliminary crystallographic analysis of the tandem tudor domain of Sgf29 from Saccharomyces cerevisiae. Acta crystallographica. Section F, Structural biology and crystallization communications 5 20693663
2026 Sgf29 regulates pluripotency by maintaining chromatin accessibility and promoting the expression of core transcription factors. Science China. Life sciences 0 41843375

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