Affinage

SUPT16H

FACT complex subunit SPT16 · UniProt Q9Y5B9

Length
1047 aa
Mass
119.9 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUPT16H (SPT16) is the large subunit of the heterodimeric FACT histone chaperone, which partners with SSRP1 to manage nucleosome dynamics during transcription, DNA replication, and repair (PMID:10421373, PMID:1922073). FACT engages nucleosomal DNA and all four core histones, and SPT16 and SSRP1 perform opposing but coordinated activities: SPT16 destabilizes nucleosomes by displacing H2A-H2B dimers — with its C-terminal domain serving as a placeholder for DNA while tethering H2A-H2B — whereas SSRP1 holds the H3-H4 tetramer on DNA and promotes dimer redeposition, allowing the complex to both disassemble and reassemble nucleosomes (PMID:31775157, PMID:30029006). The conserved SPT16 N-terminal domain adopts an enzymatically inactive aminopeptidase fold that binds the H3-H4 globular core and tails (PMID:18579787). In transcription, FACT acts at both initiation, by promoting TBP binding within a nucleosomal TATA box (PMID:15987999), and elongation, by binding the partially unraveled nucleosome generated as RNA Pol II transits and by facilitating reassembly upstream (PMID:33846633); in vivo it maintains the +1 nucleosome required for promoter-proximal Pol II pausing and productive elongation (PMID:38810649), and supports Pol I and Pol III transcription as well (PMID:19214185). FACT couples nucleosome assembly to DNA replication by depositing newly synthesized H3-H4 and recruits to the fork through a direct SPT16 N-terminal interaction with the fork-protection factor Tof1 (PMID:26804921, PMID:35061899), and is essential to sustain MCM2-7 helicase retention and ATR/CHK1 checkpoint signaling under replication stress (PMID:32533099). In DNA double-strand break repair, SUPT16H directly binds RNF20 to drive H2B ubiquitylation, chromatin relaxation, and end resection (PMID:22031019, PMID:24357716). FACT activity is further integrated with histone ubiquitin turnover through stimulation of the deubiquitinases Ubp10 and Usp7 (PMID:30681413, PMID:32894293) and with higher-order genome organization via a direct interaction with cohesin that supports TAD formation (PMID:31582854). At specific loci FACT acts repressively, acting as a barrier to cell-fate reprogramming (PMID:30078731, PMID:30319048) and supporting stress-responsive gene induction downstream of TFEB/TFE3 (PMID:35230915).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1991 High

    Established SUPT16H's yeast ortholog as an essential gene linking transcription to the cell cycle, the first functional anchor for the gene.

    Evidence Null and temperature-sensitive alleles with genetic suppression and epistasis in S. cerevisiae

    PMID:1922073

    Open questions at the time
    • Did not define a biochemical activity or partner
    • Mechanistic basis of transcriptional and cell-cycle defects unresolved
  2. 1999 High

    Defined FACT as the SPT16-SSRP1 heterodimer and showed it is a chromatin-specific elongation factor acting by nucleosome disassembly, establishing the molecular identity and core activity.

    Evidence Biochemical purification, reconstituted in vitro chromatin transcription, nucleosome/H2A-H2B binding, histone crosslinking

    PMID:10421373

    Open questions at the time
    • Structural basis of nucleosome engagement unknown
    • How disassembly is coupled to reassembly not addressed
  3. 2005 High

    Extended FACT function to transcription initiation by showing SPT16 promotes TBP loading on nucleosomal promoters, broadening its role beyond elongation.

    Evidence In vitro TBP-nucleosome reconstitution, synthetic lethality, and ChIP in yeast

    PMID:15987999

    Open questions at the time
    • Mechanism of TBP-facilitating nucleosome remodeling not structurally defined
    • Generality across promoters in metazoans untested
  4. 2008 High

    Identified the SPT16 N-terminal domain as a structurally defined H3-H4 binding module, assigning histone-binding function to a specific region.

    Evidence 2.1 Å crystal structure of Spt16-N with mutagenesis and in vitro binding (fission yeast)

    PMID:18579787

    Open questions at the time
    • Role of H3-H4 binding within the intact nucleosome cycle not shown
    • Functional necessity of the domain in vivo not defined here
  5. 2009 High

    Showed FACT operates beyond Pol II, co-purifying with and facilitating Pol I and Pol III transcription, generalizing its chromatin-elongation role.

    Evidence Co-IP, ChIP at rRNA repeats, siRNA knockdown, run-on assay in mammalian cells

    PMID:19214185

    Open questions at the time
    • Whether the SPT16 nucleosome mechanism is identical across polymerases not resolved
  6. 2009 Medium

    Demonstrated FACT-dependent nucleosome eviction at a promoter and its requirement for coactivator re-recruitment, linking chromatin disassembly to gene activation in vivo.

    Evidence Cell-cycle-resolved ChIP and genetic epistasis at the yeast HO promoter

    PMID:19481521

    Open questions at the time
    • Single-locus study; genome-wide generality not established here
    • Direct SPT16 vs SSRP1 contributions not separated
  7. 2011 Medium

    Connected SUPT16H to DNA double-strand break repair by showing it is required for RNF20-mediated H2B ubiquitylation and repair-protein loading, opening a genome-stability role.

    Evidence siRNA knockdown, co-IP, γH2AX/repair foci, HR reporter, IR sensitivity in human cells

    PMID:22031019

    Open questions at the time
    • Direct vs indirect role of SPT16 in RNF20 recruitment not fully resolved
    • Single-lab phenotypes
  8. 2013 Medium

    Confirmed and refined the DSB role, establishing direct SUPT16H-RNF20 binding and FACT-driven chromatin relaxation as upstream of efficient homologous recombination.

    Evidence Co-IP, foci imaging, HR reporter, clonogenic survival, rescue by enforced nucleosome relaxation

    PMID:24357716

    Open questions at the time
    • Structural detail of the SPT16-RNF20 interface unknown
    • How FACT senses DSB sites not defined
  9. 2016 High

    Placed FACT in replication-coupled nucleosome assembly, showing SPT16 H3-H4 binding drives deposition of new histones in concert with Rtt106 and the H3K56ac mark.

    Evidence Genetic epistasis, mutant allele binding assays, co-IP, histone deposition assay in yeast

    PMID:26804921

    Open questions at the time
    • Order of FACT vs CAF-1/Rtt106 handoff during replication not fully ordered
  10. 2018 High

    Resolved the division of labor between subunits, showing SPT16 destabilizes nucleosomes by dimer displacement while SSRP1 preserves the H3-H4 tetramer — the mechanistic core of FACT activity.

    Evidence Single-nucleosome FRET and biochemical subunit dissection

    PMID:30029006

    Open questions at the time
    • How the two opposing activities are temporally coordinated in vivo not shown
  11. 2018 Medium

    Revealed a repressive, transition-specific function by showing FACT is a barrier to cell-fate reprogramming, distinguishing it from a purely constitutive elongation factor.

    Evidence C. elegans genetic screen, human fibroblast knockdown, iPSC reprogramming, RNA-seq/ChIP-seq; CRISPR SPT16 deletion and chemical inhibition

    PMID:30078731 PMID:30319048

    Open questions at the time
    • Molecular basis of locus-specific repression vs activation unclear
    • Why FACT requirement is transient during state transitions undefined
  12. 2019 High

    Provided the structural mechanism of nucleosome engagement, showing FACT CTDs gate DNA binding and SPT16 CTD acts as a DNA placeholder tethering H2A-H2B.

    Evidence Two cryo-EM structures of human FACT-subnucleosome plus HDX-MS and biochemistry

    PMID:31775157

    Open questions at the time
    • Dynamics of conformational switching in real time not captured
    • Structure on a fully transcribing complex not in this study
  13. 2019 High

    Integrated FACT with histone-ubiquitin turnover and chromatin homeostasis, linking it to deubiquitinase stimulation, antisense suppression, histone recycling, and genome architecture.

    Evidence In vitro deubiquitination, genetic epistasis, RNA-seq/ChIP-seq/nucleosome mapping, co-IP and Hi-C across yeast and human studies

    PMID:30681413 PMID:31365865 PMID:31582854 PMID:31837996

    Open questions at the time
    • Whether cohesin and H2Bub effects share a common SPT16 surface unknown
    • Direct vs indirect contribution to TAD formation not separated
  14. 2019 Medium

    Connected FACT to transcription-coupled DSB responses and DNA-structure sensing, with OTUD5-SPT16 driving Pol II arrest and SSRP1 recognizing Z-DNA-prone sequences to trigger p53.

    Evidence DUB RNAi screen, co-IP, RNA synthesis assays; in vitro DNA binding and curaxin ChIP with p53 readout

    PMID:28082391 PMID:30508113

    Open questions at the time
    • Whether SPT16 or SSRP1 is the primary structural sensor not resolved
    • Physiological prevalence of Z-DNA sensing unclear
  15. 2020 Medium

    Established FACT as essential for surviving replication stress by maintaining MCM2-7 retention and enabling ATR/CHK1 checkpoint activation.

    Evidence Knockdown/knockout, chromatin fractionation, RPA imaging, checkpoint phospho-analysis, DNA fiber assay in mammalian cells

    PMID:32533099

    Open questions at the time
    • Direct vs chromatin-mediated effect on MCM retention not distinguished
    • Single-lab findings
  16. 2021 High

    Visualized FACT acting during active Pol II transcription, showing it binds partially unraveled nucleosomes and excludes Chd1/Spt5 to position reassembly upstream.

    Evidence Cryo-EM of yeast Pol II-Spt4/5-nucleosome complexes and in vitro transcription reconstitution

    PMID:33846633

    Open questions at the time
    • Kinetic coupling between Pol II passage and FACT reassembly not measured
  17. 2022 High

    Defined domain-specific recruitment of FACT to the replication fork via SPT16 N-terminus-Tof1 interaction, and showed nucleosome reorganization requires the middle and C-terminal domains.

    Evidence Single-molecule FRET, structure-guided pulldowns, in vitro chromatin replication

    PMID:35061899

    Open questions at the time
    • Whether the analogous SPT16-fork interaction operates in human cells not shown here
  18. 2022 Medium

    Linked FACT to metabolic and stress signaling, with PKM2-derived pyruvate binding SSRP1 to enhance γH2AX chromatin loading, and FACT acting downstream of TFEB/TFE3 to remodel stress-gene promoters.

    Evidence Co-IP, in vitro binding, γH2AX loading assays, phospho-mutant analysis; co-IP, knockdown/inhibitor, ChIP, RT-qPCR

    PMID:35048565 PMID:35230915

    Open questions at the time
    • Direct SPT16 contribution to these signaling interactions not isolated from SSRP1
    • Single-lab studies
  19. 2024 High

    Demonstrated in vivo that FACT maintains chromatin architecture required for promoter-proximal Pol II pausing and productive elongation, anchoring the mechanism in human cells.

    Evidence Auxin-inducible rapid FACT depletion with PRO-seq, ChIP-seq, RNA-seq, ATAC/MNase-seq

    PMID:38810649

    Open questions at the time
    • Direct mechanism linking +1 nucleosome maintenance to pause stability not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FACT's distinct activities — disassembly, reassembly, repressive locus-specific control, repair, and architectural roles — are selectively deployed and regulated at individual genomic sites in vivo remains unresolved.
  • No unified model for context-dependent targeting
  • Regulation distinguishing activating vs repressive FACT function unknown
  • Structural basis of repair-specific partner interactions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 4 GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-69306 DNA Replication 3 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 1
Partners
NEK9OTUD5PKM2RNF20SSRP1TFEBTOF1USP7
Complex memberships
FACT complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 FACT complex comprises human SPT16 (SUPT16H, homologue of yeast Spt16/Cdc68) and SSRP1 proteins; FACT specifically interacts with nucleosomes and histone H2A/H2B dimers and functions as a chromatin-specific transcription elongation factor required for transcription of chromatin templates in vitro; FACT activity is abrogated by covalent crosslinking of nucleosomal histones, indicating it works by promoting nucleosome disassembly. Biochemical purification, reconstituted in vitro transcription on chromatin templates, direct binding assays (nucleosome and H2A/H2B interaction), crosslinking experiments Nature High 10421373
1991 SPT16/CDC68 (yeast orthologue of SUPT16H) is an essential gene in S. cerevisiae required for normal transcription at multiple loci; temperature-sensitive spt16 alleles suppress delta insertion mutations and upstream activating sequence deletions, demonstrating a role in promoter function; SPT16 is identical to CDC68, previously shown to be required for passage through cell-cycle START, but transcriptional effects of spt16 mutations are at least partially independent of cell-cycle arrest. Null mutation construction, temperature-sensitive allele isolation, genetic suppression assays, epistasis analysis Molecular and cellular biology High 1922073
2008 The N-terminal 'peptidase homology' domain of fission yeast Spt16 (Spt16-N) is a histone H3-H4 binding module; crystal structure at 2.1 Å reveals an aminopeptidase P fold that has lost enzymatic activity but directly binds the globular core domains and N-terminal tails of H3-H4; mutations in a conserved surface pocket in Spt16-N or posttranslational modification of the H4 tail reduce interaction in vitro. X-ray crystallography (2.1 Å), biochemical binding assays, site-directed mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 18579787
2019 Cryo-EM structures of human FACT (SPT16/SSRP1) in complex with partially assembled subnucleosomes reveal: (1) FACT engages extensively with nucleosomal DNA and all histone variants; (2) the C-terminal domains (CTDs) of both SPT16 and SSRP1 protect the DNA-binding surface; (3) interaction with H2A-H2B releases this inhibition allowing FACT-H2A-H2B to dock onto a DNA/H3-H4 complex; (4) SPT16 CTD acts as a placeholder for DNA by tethering H2A-H2B; (5) SSRP1 can adopt two conformations depending on whether a second H2A-H2B dimer is present. This mechanism facilitates H2A-H2B dimer removal, stabilizes subnucleosomal intermediates, and promotes reassembly. Cryo-electron microscopy (two structures), hydrogen-deuterium exchange mass spectrometry, biochemical binding assays Nature High 31775157
2018 SPT16 (large subunit of FACT) destabilizes the nucleosome by displacing H2A/H2B dimers at the single-nucleosome level, while SSRP1 (small subunit) maintains nucleosome integrity by holding the H3/H4 tetramer on DNA and promoting deposition of H2A/H2B dimers; the two subunits thus play opposing but coordinated roles in nucleosome remodeling. Single-nucleosome FRET, biochemical reconstitution, subunit-specific functional dissection Molecular cell High 30029006
2021 Cryo-EM structures of transcribing yeast RNA Pol II-Spt4/5-nucleosome complexes show that FACT binds a partially unraveled nucleosome generated during Pol II transcription, excludes Chd1 and Spt5, and is positioned to facilitate nucleosome reassembly upstream; biochemically, FACT facilitates Pol II transcription through a nucleosome when Spt4/5 and TFIIS are present. Cryo-electron microscopy, in vitro transcription reconstitution on chromatin templates Nature structural & molecular biology High 33846633
2009 FACT (SSRP1 and SPT16 subunits) co-purifies and co-immunoprecipitates with mammalian RNA Pol I complexes; SSRP1 is detectable at rRNA gene repeats by ChIP; siRNA knockdown of FACT subunits reduces 47S pre-rRNA levels without affecting synthesis of the first 40 nt of rRNA, placing FACT function specifically at Pol I elongation through chromatin. FACT also associates with Pol III complexes and facilitates Pol III-transcribed gene expression. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), siRNA knockdown, run-on transcription assay The EMBO journal High 19214185
2005 Yeast FACT (yFACT) promotes TBP binding to a TATA box within a reconstituted nucleosome in a TFIIA-dependent manner in vitro; in vivo, certain spt16 mutations are synthetically lethal with TBP and TFIIA (TOA2) mutants, and spt16 mutations reduce TBP binding to promoters by ChIP, establishing a role for SPT16 in transcription initiation as well as elongation. In vitro TBP-nucleosome binding reconstitution, genetic synthetic lethality, chromatin immunoprecipitation (ChIP) Molecular and cellular biology High 15987999
2009 At the yeast HO promoter, FACT (SPT16-containing complex) is required for nucleosome eviction at distinct promoter regions; FACT and Asf1 bind upstream HO promoter elements before transcription initiation and are both required for re-recruitment of Swi/Snf, SAGA, and Mediator coactivators to promoter-proximal regions. Chromatin immunoprecipitation (ChIP), genetic epistasis with chromatin modifier mutants, cell-cycle-resolved ChIP analysis Molecular cell Medium 19481521
2016 FACT (Spt16-Pob3 in yeast) promotes newly synthesized histone H3-H4 deposition during DNA replication-coupled nucleosome assembly; an spt16 allele (spt16-m) defective in H3-H4 binding impairs their deposition; FACT physically associates with Rtt106 and the H3K56 acetylation mark on newly synthesized H3 modulates this interaction; FACT shows synthetic defects with CAF-1 and Rtt106. Genetic epistasis (synthetic lethality), in vitro H3-H4 binding assays, co-immunoprecipitation, site-directed mutagenesis, histone deposition assay Cell reports High 26804921
2011 SUPT16H (SPT16, a FACT subunit) is required for RNF20-mediated H2B ubiquitylation at sites of DNA double-strand breaks; depletion of SUPT16H causes defective accumulation of repair proteins (RAD51, BRCA1), decreased H3K56ac, sustained γH2AX phosphorylation, impaired DNA end resection, delayed DSB repair, and decreased recruitment of SNF2h; SUPT16H directly binds RNF20 in vivo; PAF1 is dispensable for DNA damage-induced SUPT16H-RNF20 interaction. siRNA knockdown, co-immunoprecipitation, γH2AX foci imaging, H3K56ac quantification, homologous recombination reporter assay, ionizing radiation sensitivity Cell cycle (Georgetown, Tex.) Medium 22031019
2013 SUPT16H (FACT) is required for RNF20 recruitment to DNA double-strand break sites and subsequent H2B ubiquitylation; SUPT16H directly binds RNF20 in vivo and is required for SNF2h accumulation and chromatin relaxation at DSBs; SUPT16H depletion causes radiation and mitomycin-C sensitivity and decreased homologous recombination activity; enforced nucleosome relaxation counteracts SUPT16H-deficient phenotypes. siRNA knockdown, co-immunoprecipitation, immunofluorescence foci assays, HR reporter assay, clonogenic survival assay Journal of cell science Medium 24357716
2003 FACT (Spt16 subunit) forms a stable ~600 kDa complex with the kinase Nek9 in interphase nuclei; when complexed with FACT, Nek9 exhibits elevated phosphorylation on Thr210 (activation loop); Nek9 RNAi causes defects in G1 and S phase progression, phenotypically linked to the phospho-Nek9-FACT complex formation. Co-immunoprecipitation, size-exclusion chromatography, phosphorylation analysis, RNA interference cell-cycle analysis The Journal of biological chemistry Medium 14660563
2004 Domain organization of yeast FACT: FACT integrity depends on Pob3 interactions with the Spt16 Mid domain; the conserved Spt16 N-terminal domain (NTD) is dispensable for normal growth but becomes important under replication stress conditions; genetic interactions suggest some Spt16 NTD functions are partially redundant within FACT. Genetic analysis (deletion alleles, synthetic lethality), biochemical fractionation Nucleic acids research Medium 15520471
2017 FACT (via its SSRP1 subunit/CID domain) binds Z-DNA or DNA in transition from B to Z form in cells treated with curaxin; purified SSRP1 CID domain binds methylated alternating purine/pyrimidine DNA (prone to Z-DNA transition) more strongly than other DNA types in vitro; FACT binding to these alternative DNA structure regions triggers a p53 response, positioning FACT as a sensor of DNA torsional stress. ChIP after curaxin treatment, in vitro DNA binding assays with purified SSRP1/CID, p53 response assay Nucleic acids research Medium 28082391
2015 SUPT16H (SPT16) interacts with HIV-1 Tat protein (but not SSRP1); both SUPT16H and SSRP1 are recruited to the HIV-1 LTR promoter; SUPT16H presence interferes with Cyclin T1 (P-TEFb subunit) association with the Tat-LTR axis; depletion of SUPT16H or SSRP1 enhances Tat-mediated LTR activity, affects transcriptional initiation and elongation, and spontaneously reverses HIV-1 latency in cell models. Co-immunoprecipitation, ChIP, RNAi knockdown, HIV-1 latency reactivation assay, LTR reporter assay The Journal of biological chemistry Medium 26378236
2019 FACT stimulates Ubp10 deubiquitinase activity specifically on nucleosome substrates (not other substrates); a FACT mutant strain shows elevated H2B monoubiquitination in vivo; combination of FACT mutants with deletion of Ubp10 (but not Ubp8) confers increased sensitivity to hydroxyurea and activates cryptic transcription, indicating FACT and Ubp10 coordinate nucleosome assembly during DNA replication and transcription. In vitro deubiquitination assay with reconstituted nucleosomes, H2B-Ub immunoblotting in FACT mutant strains, genetic epistasis (double mutants), cryptic transcription reporter assay eLife High 30681413
2019 FACT globally represses antisense transcripts near the 5' end of genes in S. pombe; H2B ubiquitination (H2Bub) is required for FACT activity in genic regions—in the H2Bub mutant, FACT binding to chromatin is altered and its association with histones stabilized, leading to reduction of genic nucleosomes; FACT depletion globally restores nucleosomes lost in the H2Bub mutant; FACT (specifically Spt16 subunit absent Pob3) also controls the 3' end processing of genes and maintains nucleosomes in subtelomeric regions required for their compaction. RNA-seq, ChIP-seq, genome-wide nucleosome mapping, genetic (H2Bub mutant and FACT depletion), co-immunoprecipitation, microscopy Molecular cell High 31837996
2019 FACT mediates cohesin function on chromatin: FACT interacts directly with cohesin, is dynamically required for cohesin localization on chromatin; depletion of FACT in metaphase cells prevents cohesin accumulation at pericentric regions and reduces binding on chromosome arms; FACT depletion reduces cohesin-dependent TAD-like structures in both G1 and metaphase chromosomes by Hi-C, although sister chromatid cohesion itself is intact. Co-immunoprecipitation (FACT-cohesin), ChIP-seq (cohesin localization), Hi-C (TAD analysis), conditional FACT depletion Nature structural & molecular biology High 31582854
2019 OTUD5 deubiquitinase interacts with FACT component SPT16 and antagonizes H2A deposition at DNA double-strand break lesions; OTUD5-SPT16 interaction (along with OTUD5-UBR5 interaction) is required for arresting RNA Pol II elongation at DSB lesions; a cancer-associated missense mutation in OTUD5 UIM abrogates FACT association and Pol II arrest. DUB RNAi screen, co-immunoprecipitation, immunofluorescence, RNA synthesis assay at DSBs Nucleic acids research Medium 30508113
2019 FACT and Spt6 are required for local recycling of modified histones during transcription in S. cerevisiae; disruption of FACT or Spt6 causes nucleosome loss that is partially compensated by non-transcription-coupled chaperones; in the absence of functional FACT or Spt6, transcription-evicted modified histones are randomly incorporated, scrambling epigenomic information. ChIP-seq for histone modifications in FACT/Spt6 mutant strains, nucleosome mapping, genetic analysis Cell reports Medium 31365865
2018 FACT acts as a barrier to cell fate reprogramming in C. elegans and humans: FACT depletion in C. elegans identified in a genetic screen as maintaining cell identity; FACT depletion enhances reprogramming of human fibroblasts to iPSCs; a subset of FACT-occupied genes (including reprogramming-promoting factors) shows increased expression upon FACT depletion, revealing a repressive function of FACT at specific loci. Genetic screen (C. elegans), siRNA/shRNA knockdown, iPSC reprogramming efficiency assay, RNA-seq, ChIP-seq Developmental cell Medium 30078731
2020 FACT is essential to overcome replication stress in mammalian cells: in the absence of FACT during replication stress, the MCM2-7 helicase dissociates from chromatin, resulting in absence of ssDNA accumulation, RPA binding, and ATR/CHK1 checkpoint activation; without this response, stalled replication forks are not stabilized, new origin firing is not prevented, and DNA damage and cell death accumulate. Genetic knockdown/knockout, chromatin fractionation (MCM2-7 dissociation), RPA immunofluorescence, ATR/CHK1 phosphorylation analysis, DNA fiber assay, hydroxyurea/APH treatment Oncogene Medium 32533099
2022 FACT (SSRP1 and SUPT16H) interacts with transcription factors TFEB and TFE3 in the nucleus upon nutrient deprivation or oxidative stress; FACT depletion (siRNA or curaxin inhibitor) does not affect TFEB activation, stability, or promoter binding, but severely impairs induction of antioxidant and lysosomal target genes; FACT is required downstream of TFEB/TFE3 binding for chromatin remodeling at stress-responsive gene promoters. Co-immunoprecipitation, siRNA knockdown, curaxin inhibitor treatment, RT-qPCR, ChIP Autophagy Medium 35230915
2022 Recruitment of FACT to the replication fork requires the N-terminal domain of Spt16, which directly interacts with the fork protection complex subunit Tof1; single-molecule FRET demonstrates that nucleosomal DNA reorganization by FACT requires coordinated engagement by the middle and C-terminal domains of Spt16 and Pob3 (but not Spt16 N-terminus); this Tof1-Spt16 NTD interaction is required for robust in vitro chromatin replication. Single-molecule FRET, structure-guided pulldowns, in vitro chromatin replication assay Nucleic acids research High 35061899
2022 Pyruvate produced by PKM2 directly binds SSRP1 subunit of the FACT complex, increasing FACT association with γH2AX and facilitating FACT-mediated chromatin loading of γH2AX to promote DNA repair; PKM2 is phosphorylated at S222 upon DNA damage and interacts with the FACT complex (SPT16 and SSRP1); exogenous pyruvate supplementation is sufficient to enhance FACT-mediated γH2AX chromatin loading. Co-immunoprecipitation, in vitro binding assay (pyruvate-SSRP1), γH2AX chromatin loading assay, PKM2 phospho-mutant analysis, clonogenic survival Advanced science Medium 35048565
2024 Rapid depletion of FACT from human cells in vivo destabilizes chromatin and leads to: (1) defective promoter-proximal RNA Pol II pausing dependent on the +1 nucleosome maintained by FACT; (2) elongation defects; (3) increased premature termination of Pol II; demonstrating that FACT maintains chromatin architecture in vivo to support pausing and productive elongation. Rapid auxin-inducible degron (AID) FACT depletion, multi-omics (ChIP-seq, PRO-seq, RNA-seq, ATAC-seq/MNase-seq) Molecular cell High 38810649
2020 FACT (SSRP1 subunit) recruits H2B deubiquitinase Usp7 to SSRP1 target genes in mouse ESCs; Ssrp1 interacts with MERVL retrotransposon sequences and suppresses cryptic MERVL-derived transcription; loss of Ssrp1 activates MERVL ERVs, which is rescued by Ssrp1 re-introduction; Usp7 deubiquitinates H2Bub at these loci to repress MERVL-fused gene expression. Co-immunoprecipitation (SSRP1-Usp7), ChIP, RNA-seq, SSRP1 rescue experiment, siRNA knockdown of Usp7 Nucleic acids research Medium 32894293
2018 FACT inhibition (SPT16 CRISPR deletion or small molecule inhibitor) blocks reprogramming of fibroblasts to iPSCs at an early step without affecting fibroblast viability or proliferation; FACT is not required for maintenance of established pluripotency (core pluripotency gene expression unaffected), but trypsinization and passaging transiently reintroduces a FACT requirement, suggesting FACT promotes transitions between stable chromatin states rather than acting as a constitutive elongation factor. CRISPR-mediated SPT16 deletion, small-molecule FACT inhibitor, iPSC reprogramming assay, gene expression analysis Stem cells and development Medium 30319048

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 The chromatin-specific transcription elongation factor FACT comprises human SPT16 and SSRP1 proteins. Nature 462 10421373
2006 Reversal of hepatic fibrosis -- fact or fantasy? Hepatology (Baltimore, Md.) 302 16447275
2000 Human cancer cell lines: fact and fantasy. Nature reviews. Molecular cell biology 241 11252900
2018 The proton sponge hypothesis: Fable or fact? European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 233 29859281
2003 Adult stem cell plasticity: fact or artifact? Annual review of cell and developmental biology 190 14570561
2019 FACT caught in the act of manipulating the nucleosome. Nature 182 31775157
2011 The histone chaperone FACT: structural insights and mechanisms for nucleosome reorganization. The Journal of biological chemistry 180 21454601
1991 Mutations in SPT16/CDC68 suppress cis- and trans-acting mutations that affect promoter function in Saccharomyces cerevisiae. Molecular and cellular biology 147 1922073
2022 Bystander effect of antibody-drug conjugates: fact or fiction? Current oncology reports 135 35305211
2002 Intermittent hypoxic training: fact and fancy. High altitude medicine & biology 128 12162862
2017 "Mesenchymal stem cells": fact or fiction, and implications in their therapeutic use. F1000Research 124 28491279
1999 The AT2 receptor: fact, fancy and fantasy. Regulatory peptides 123 10395404
1979 Inhibin--fact or artifact. Molecular and cellular endocrinology 121 376371
2011 Opioid receptor subtypes: fact or artifact? British journal of anaesthesia 118 21613279
2008 The FACT Spt16 "peptidase" domain is a histone H3-H4 binding module. Proceedings of the National Academy of Sciences of the United States of America 116 18579787
2021 Structural basis of nucleosome transcription mediated by Chd1 and FACT. Nature structural & molecular biology 112 33846633
2020 The role of FACT in managing chromatin: disruption, assembly, or repair? Nucleic acids research 110 33104782
2005 MDR1 genotype-related pharmacokinetics: fact or fiction? Drug metabolism and pharmacokinetics 106 16415525
2009 FACT facilitates chromatin transcription by RNA polymerases I and III. The EMBO journal 101 19214185
2001 Exercise-induced muscle damage and inflammation: fact or fiction? Acta physiologica Scandinavica 100 11412135
2021 Antiaging diets: Separating fact from fiction. Science (New York, N.Y.) 99 34793210
2018 Structure and function of the histone chaperone FACT - Resolving FACTual issues. Biochimica et biophysica acta. Gene regulatory mechanisms 97 30055319
2011 Fact and fiction in tuberculosis vaccine research: 10 years later. The Lancet. Infectious diseases 96 21798463
1999 Apocrine secretion--fact or artifact? Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 96 10560009
1999 Psychoneuroimmunology and cancer: fact or fiction? European journal of cancer (Oxford, England : 1990) 96 10673969
2000 Adverse effects of creatine supplementation: fact or fiction? Sports medicine (Auckland, N.Z.) 95 10999421
2009 FACT and Asf1 regulate nucleosome dynamics and coactivator binding at the HO promoter. Molecular cell 92 19481521
2018 Functions of FACT in Breaking the Nucleosome and Maintaining Its Integrity at the Single-Nucleosome Level. Molecular cell 91 30029006
2006 Production of interferon-gamma by myeloid cells--fact or fancy? Trends in immunology 88 16698319
2019 Histone Recycling by FACT and Spt6 during Transcription Prevents the Scrambling of Histone Modifications. Cell reports 87 31365865
2003 Transdifferentiation--fact or artifact. Journal of cellular biochemistry 84 12461772
2017 FACT is a sensor of DNA torsional stress in eukaryotic cells. Nucleic acids research 81 28082391
2005 The yeast FACT complex has a role in transcriptional initiation. Molecular and cellular biology 81 15987999
2016 The Histone Chaperone FACT Contributes to DNA Replication-Coupled Nucleosome Assembly. Cell reports 75 26804921
2011 Antioxidant therapy in male infertility: fact or fiction? Asian journal of andrology 75 21516118
2005 Tumor counterattack: fact or fiction? Cancer immunology, immunotherapy : CII 72 15889255
2005 Geologically ancient DNA: fact or artefact? Trends in microbiology 71 15866038
2018 FACT Sets a Barrier for Cell Fate Reprogramming in Caenorhabditis elegans and Human Cells. Developmental cell 67 30078731
2005 Mycoplasma host specificity: fact or fiction? Veterinary journal (London, England : 1997) 66 16266844
2019 Sulfonamide Hypersensitivity: Fact and Fiction. The journal of allergy and clinical immunology. In practice 65 31495421
2014 Helicobacter pylori infection and diabetes: is it a myth or fact? World journal of gastroenterology 65 24782613
2011 The H2B ubiquitin ligase RNF40 cooperates with SUPT16H to induce dynamic changes in chromatin structure during DNA double-strand break repair. Cell cycle (Georgetown, Tex.) 65 22031019
1997 The M5 (m5) receptor subtype: fact or fiction? Life sciences 65 9121354
2019 The OTUD5-UBR5 complex regulates FACT-mediated transcription at damaged chromatin. Nucleic acids research 62 30508113
2013 Epigenetics of progression of chronic kidney disease: fact or fantasy? Seminars in nephrology 62 24011578
2005 Indeterminate cell histiocytosis: fact or fiction? Journal of cutaneous pathology 61 16115054
2011 Quasispecies as a matter of fact: viruses and beyond. Virus research 60 21945638
2022 Human age reversal: Fact or fiction? Aging cell 59 35778957
2012 Individualized targeted therapy for glioblastoma: fact or fiction? Cancer journal (Sudbury, Mass.) 59 22290256
2008 FACT and the reorganized nucleosome. Molecular bioSystems 57 18931784
2002 Immunoglobulin G subclass deficiency: fact or fancy? Current allergy and asthma reports 57 12165200
2011 Facultative stem cells in liver and pancreas: fact and fancy. Developmental dynamics : an official publication of the American Association of Anatomists 56 21312313
2011 High platelet reactivity and clinical outcome - fact and fiction. Thrombosis and haemostasis 55 21505714
2016 Cofactor squelching: Artifact or fact? BioEssays : news and reviews in molecular, cellular and developmental biology 54 27273739
2005 Bell's palsy and Herpes simplex virus: fact or mystery? Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 54 15699730
2013 Histone chaperone FACT regulates homologous recombination by chromatin remodeling through interaction with RNF20. Journal of cell science 53 24357716
2016 Nucleus pulposus phenotypic markers to determine stem cell differentiation: fact or fiction? Oncotarget 52 26735178
2017 Fact or fiction: updates on how protein-coding genes might emerge de novo from previously non-coding DNA. F1000Research 51 28163910
2015 Interaction between periodontal disease and atherosclerotic vascular disease--Fact or fiction? Atherosclerosis 50 26100678
2011 Imaging the high-affinity state of the dopamine D2 receptor in vivo: fact or fiction? Biochemical pharmacology 50 21945484
2012 Renal stem cells: fact or science fiction? The Biochemical journal 49 22574774
2020 Histone chaperone FACT FAcilitates Chromatin Transcription: mechanistic and structural insights. Current opinion in structural biology 47 32574979
1999 Nongenomic steroid actions: fact or fantasy? Vitamins and hormones 46 10232053
2015 FACT Proteins, SUPT16H and SSRP1, Are Transcriptional Suppressors of HIV-1 and HTLV-1 That Facilitate Viral Latency. The Journal of biological chemistry 45 26378236
2010 Policosanols as nutraceuticals: fact or fiction. Critical reviews in food science and nutrition 45 20301014
2003 Nek9, a novel FACT-associated protein, modulates interphase progression. The Journal of biological chemistry 44 14660563
2017 N,N-dimethyltryptamine and the pineal gland: Separating fact from myth. Journal of psychopharmacology (Oxford, England) 43 29095071
2013 The role of FACT in making and breaking nucleosomes. Biochimica et biophysica acta 43 24459727
2005 Hairy cell leukemia variant: fact or fiction. American journal of clinical pathology 42 15762289
2004 Domain organization of the yeast histone chaperone FACT: the conserved N-terminal domain of FACT subunit Spt16 mediates recovery from replication stress. Nucleic acids research 42 15520471
1999 Vaccines and diagnostic methods for bovine mastitis: fact and fiction. Advances in veterinary medicine 41 9890021
1997 Fact and artefact in confocal microscopy. Advances in dental research 41 9470501
2022 Pyruvate Facilitates FACT-Mediated γH2AX Loading to Chromatin and Promotes the Radiation Resistance of Glioblastoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 39 35048565
2022 The fork protection complex recruits FACT to reorganize nucleosomes during replication. Nucleic acids research 39 35061899
1998 The euryarchaeotes, a subdomain of Archaea, survive on a single DNA polymerase: fact or farce? Genes & genetic systems 38 10333564
2019 The Chaperone FACT and Histone H2B Ubiquitination Maintain S. pombe Genome Architecture through Genic and Subtelomeric Functions. Molecular cell 37 31837996
2015 Dysplastic nevus: Fact and fiction. Journal of the American Academy of Dermatology 36 26037217
2019 HDL: Fact, fiction, or function? HDL cholesterol and cardiovascular risk. European journal of preventive cardiology 34 33838035
2014 The role of stem cells in aesthetic surgery: fact or fiction? Plastic and reconstructive surgery 34 24732654
2004 Immune effect of hypertonic saline: fact or fiction? Acta anaesthesiologica Scandinavica 34 15196097
2019 FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics. eLife 32 30681413
2006 Gene therapy for erectile dysfunction: fact or fiction? European urology 32 16950560
2005 Idiopathic midline destructive disease: fact or fiction. Oral oncology 32 15792605
2020 The FACT Histone Chaperone: Tuning Gene Transcription in the Chromatin Context to Modulate Plant Growth and Development. Frontiers in plant science 31 32140163
2012 Pharma-metabolomics in neonatology: is it a dream or a fact? Current pharmaceutical design 31 22564294
2016 Targeting Nanocarriers with Anisamide: Fact or Artifact? Advanced materials (Deerfield Beach, Fla.) 30 27885719
1998 Life's third domain (Archaea): an established fact or an endangered paradigm? Theoretical population biology 30 9733652
2024 FACT maintains chromatin architecture and thereby stimulates RNA polymerase II pausing during transcription in vivo. Molecular cell 29 38810649
2012 Peripheral modulation of smell: fact or fiction? Seminars in cell & developmental biology 29 22986099
2022 Sodium-glucose cotransporter inhibition in polycystic kidney disease: fact or fiction. Clinical kidney journal 28 35756735
2020 Histone chaperone FACT represses retrotransposon MERVL and MERVL-derived cryptic promoters. Nucleic acids research 28 32894293
2013 Fact or fiction--identifying the elusive multiple myeloma stem cell. Journal of hematology & oncology 28 24314019
2022 The histone chaperone FACT: a guardian of chromatin structure integrity. Transcription 27 35485711
2019 FACT mediates cohesin function on chromatin. Nature structural & molecular biology 27 31582854
2020 Histone chaperone FACT is essential to overcome replication stress in mammalian cells. Oncogene 26 32533099
2018 Disseminated intravascular coagulation: is it fact or fancy? Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 25 29621007
2004 The FACT chromatin modulator: genetic and structure/function relationships. Biochemistry and cell biology = Biochimie et biologie cellulaire 25 15284894
2018 FACT Inhibition Blocks Induction But Not Maintenance of Pluripotency. Stem cells and development 24 30319048
2022 The FACT complex facilitates expression of lysosomal and antioxidant genes through binding to TFEB and TFE3. Autophagy 23 35230915
2002 Nutrition and sports supplements: fact or fiction. Journal of clinical gastroenterology 23 12352292

Missed literature

Know a paper Affinage missed for SUPT16H? Flag it for the maintainers and the community.

No submissions yet.