Affinage

SUPT16H

FACT complex subunit SPT16 · UniProt Q9Y5B9

Round 2 corrected
Length
1047 aa
Mass
119.9 kDa
Annotated
2026-04-28
130 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUPT16H is the large subunit of the FACT (Facilitates Chromatin Transcription) histone chaperone complex, which together with SSRP1 reorganizes nucleosomes to enable RNA polymerase II elongation through chromatin, DNA replication, and DNA repair. FACT destabilizes nucleosomes by removing one H2A-H2B dimer during Pol II passage and re-deposits histones behind the polymerase; the SPT16 N-terminal domain binds H3-H4 through an inactive aminopeptidase fold, while the acidic C-terminus is required for H2A-H2B chaperone activity (PMID:12934006, PMID:18579787, PMID:33846633). FACT is recruited to replication forks by Tof1, to DNA double-strand breaks via RNF40-mediated H2B ubiquitination where it enables homologous recombination by facilitating RNF20 recruitment and chromatin remodeling, and to heterochromatin through HP1/Swi6 interactions (PMID:35061899, PMID:24357716, PMID:34407404). Acute FACT depletion destabilizes the +1 nucleosome and disrupts promoter-proximal Pol II pausing independently of NELF, and FACT additionally acts as a barrier to cell fate reprogramming and cooperates with TFEB/TFE3 for stress-responsive transcription (PMID:38810649, PMID:30078731, PMID:35230915).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1991 High

    Yeast genetic studies established SPT16/CDC68 as an essential gene required for normal transcription at many loci, placing it as a general chromatin-level transcriptional regulator before its biochemical activity was known.

    Evidence Null and temperature-sensitive mutant analysis with genetic suppression assays in S. cerevisiae

    PMID:1922073

    Open questions at the time
    • No biochemical mechanism defined
    • No identification of interacting partners or histone substrates
  2. 1999 High

    Biochemical reconstitution revealed that FACT (SPT16/SSRP1) facilitates Pol II elongation through nucleosomes by interacting with H2A-H2B dimers and promoting nucleosome disassembly, answering how Pol II overcomes the nucleosomal barrier.

    Evidence In vitro chromatin transcription reconstitution, nucleosome-binding assays, chemical crosslinking (HeLa extracts)

    PMID:10421373 PMID:9489704

    Open questions at the time
    • Stoichiometry of H2A-H2B removal not resolved
    • Whether FACT can reassemble nucleosomes not yet tested
  3. 2003 High

    The mechanism of FACT-mediated nucleosome traversal was defined: FACT removes one H2A-H2B dimer during Pol II passage and possesses intrinsic histone chaperone (deposition) activity, requiring the acidic C-terminus of SPT16, establishing FACT as a bidirectional histone chaperone.

    Evidence In vitro reconstituted chromatin transcription, histone deposition assays, subunit deletion/mutation analysis

    PMID:12934006

    Open questions at the time
    • Structural basis of dimer removal unknown
    • How reassembly is coordinated with elongation unclear
  4. 2006 High

    A functional loop between FACT and histone modifications was revealed: H2B monoubiquitination by RNF20/40 stimulates FACT-mediated elongation, while FACT associates with centromeric CENP-A nucleosomes, broadening its roles beyond canonical transcription.

    Evidence Reconstituted in vitro chromatin transcription; AP-MS of CENP-A nucleosome complexes

    PMID:16622419 PMID:16713563

    Open questions at the time
    • Whether H2B-Ub directly alters FACT-nucleosome affinity or acts indirectly not resolved
    • Functional role of FACT at centromeres not directly tested
  5. 2008 High

    The structural basis for FACT-histone recognition was established: the SPT16 N-terminal domain adopts an inactive aminopeptidase fold that binds H3-H4 globular domains and tails, while H2A monoubiquitination was identified as an opposing mark that excludes FACT from promoters.

    Evidence X-ray crystallography (2.1 Å), mutagenesis, in vitro binding; ChIP and RNAi in human cells

    PMID:18206970 PMID:18579787

    Open questions at the time
    • Full-length FACT-nucleosome structure lacking
    • How H2A-Ub physically prevents FACT binding not structurally resolved
  6. 2009 Medium

    FACT's role at promoters was clarified: it is required for nucleosome disassembly at promoter regions (HO, PHO5) prior to gene activation, expanding its function from elongation to transcriptional initiation.

    Evidence ChIP and genetic mutant analysis at specific yeast promoters

    PMID:19481521 PMID:19574230

    Open questions at the time
    • Whether promoter disassembly function is conserved in mammals not shown
    • How FACT is targeted to specific promoters unclear
  7. 2013 Medium

    FACT was placed upstream in the homologous recombination repair pathway: it directly recruits RNF20 to DSB sites, enabling H2B ubiquitylation, SNF2h loading, and subsequent BRCA1/RAD51 accumulation, answering how chromatin is remodeled at damage sites.

    Evidence Co-IP, siRNA knockdown, immunofluorescence at laser-induced DSBs, HR activity assays

    PMID:22031019 PMID:24357716

    Open questions at the time
    • Structural basis of FACT-RNF20 interaction not defined
    • Whether FACT participates in non-homologous end joining not tested
  8. 2019 Medium

    FACT was connected to histone deubiquitination and damage-site transcription regulation: it stimulates Ubp10-mediated H2B deubiquitination on nucleosomes and interacts with OTUD5 at DSBs to arrest Pol II elongation at damaged chromatin, revealing FACT as a coordinator of histone ubiquitin turnover.

    Evidence In vitro deubiquitination assays with nucleosome substrates, yeast genetic interactions; DUB RNAi screen, Co-IP, laser micro-irradiation in human cells

    PMID:30508113 PMID:30681413

    Open questions at the time
    • Whether FACT-Ubp10 interaction is direct or mediated by nucleosome context not resolved
    • Relative contributions of OTUD5-FACT vs other pathways to transcriptional arrest unclear
  9. 2021 High

    Cryo-EM structures captured FACT engaging a partially unraveled nucleosome during Pol II transcription and revealed that FACT recruitment requires Spt4/5 and triggers histone transfer to upstream DNA, providing the first structural visualization of the elongation-coupled nucleosome reorganization mechanism.

    Evidence Cryo-EM of Pol II-Spt4/5-nucleosome-FACT complexes, in vitro reconstituted transcription

    PMID:33846633

    Open questions at the time
    • Human FACT-nucleosome cryo-EM structure not yet available
    • How FACT disengages after histone transfer not captured
  10. 2022 Medium

    Multiple recruitment mechanisms to replication forks, stress-responsive promoters, and damage sites were defined: Tof1 recruits FACT to replication forks via the Spt16 N-terminus; FACT cooperates with TFEB/TFE3 for lysosomal/antioxidant gene induction; and pyruvate-bound SSRP1 facilitates γH2AX chromatin loading.

    Evidence Single-molecule FRET and in vitro replication; Co-IP, siRNA, curaxin treatment; PKM2-SSRP1 binding assays

    PMID:35048565 PMID:35061899 PMID:35230915

    Open questions at the time
    • Whether Tof1-FACT recruitment mechanism is conserved in metazoans not shown
    • Physiological significance of pyruvate-SSRP1 interaction outside glioblastoma unknown
  11. 2024 High

    Acute FACT depletion from human cells demonstrated that FACT maintains the +1 nucleosome required for promoter-proximal Pol II pausing independently of NELF, establishing FACT as a direct architectural regulator of the pausing checkpoint.

    Evidence Rapid degron-mediated depletion with ChIP-seq, PRO-seq, RNA-seq in human cells

    PMID:38810649

    Open questions at the time
    • How FACT distinguishes +1 nucleosomes from other nucleosomes mechanistically unclear
    • Whether pausing defect is the primary cause of premature termination or a parallel consequence not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full structural model of human FACT bound to a nucleosome during active transcription or replication is still lacking, and the mechanism by which FACT selectively targets specific genomic loci (promoters, +1 nucleosomes, DSBs, heterochromatin) rather than acting globally remains unresolved.
  • No human FACT-nucleosome cryo-EM or crystal structure
  • Locus-specific targeting mechanism unknown
  • Relative in vivo contributions of transcription-coupled vs replication-coupled FACT functions not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 4 GO:0140110 transcription regulator activity 3 GO:0044183 protein folding chaperone 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 3
Pathway
R-HSA-4839726 Chromatin organization 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-73894 DNA Repair 4 R-HSA-69306 DNA Replication 1 R-HSA-9612973 Autophagy 1
Partners
HP1/SWI6OTUD5RNF20RNF40SSRP1TFE3TFEBTOF1
Complex memberships
FACT complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 FACT (containing SPT16/SUPT16H) was purified as a novel factor that facilitates transcript elongation through nucleosomes by RNA polymerase II in vitro, acting subsequent to transcription initiation to release Pol II from a nucleosome-induced block to productive transcription. In vitro chromatin transcription reconstitution with purified factors from HeLa nuclear extract Cell High 9489704
1999 FACT comprises human SPT16 (SUPT16H), a homologue of yeast Spt16/Cdc68, and SSRP1; FACT specifically interacts with nucleosomes and histone H2A/H2B dimers, and its activity is abrogated by covalently crosslinking nucleosomal histones, indicating it promotes nucleosome disassembly during transcription elongation. Biochemical purification, Co-IP, in vitro chromatin transcription, nucleosome-binding assays, chemical crosslinking Nature High 10421373
1991 SPT16/CDC68 (yeast ortholog of SUPT16H) is essential for growth and is required for normal transcription of many loci in S. cerevisiae; spt16 mutations suppress delta insertion mutations, UAS deletions, and trans-acting mutations required for SUC2 and Ty expression, placing SPT16 as a general chromatin-level transcriptional regulator. Null and temperature-sensitive mutant analysis, genetic suppression assays in yeast Molecular and cellular biology High 1922073
2003 FACT (SUPT16H/SSRP1) facilitates Pol II-driven transcription by destabilizing nucleosomal structure such that one histone H2A-H2B dimer is removed during enzyme passage; FACT also possesses intrinsic histone chaperone activity enabling core histone deposition onto DNA. Activity requires both subunits and depends on the highly acidic C-terminus of SPT16. In vitro chromatin transcription reconstitution, histone deposition assays, subunit deletion/mutation analysis Science High 12934006
2004 Domain organization of yeast Spt16 (SUPT16H ortholog): the conserved N-terminal domain (NTD) is dispensable for normal growth but essential under replication stress; FACT integrity depends on Pob3 interactions with the Spt16 Mid domain; each FACT subunit is a multidomain protein. Genetic analysis, domain deletion mutants, biochemical interaction assays in yeast Nucleic acids research Medium 15520471
2006 Histone H2B monoubiquitination by RNF20/40 is dependent on PAF complex and FACT; H2B monoubiquitination in turn facilitates FACT function to stimulate transcript elongation by Pol II through the nucleosomal barrier in a reconstituted chromatin-transcription system. Reconstituted in vitro chromatin transcription with purified components, in vivo corroboration Cell High 16713563
2006 FACT (containing SUPT16H) is stably recruited to CENP-A nucleosomes at centromeres independently of the CENP-A NAC, as revealed by proteomic analysis of the centromeric nucleosome-associated complex, implicating FACT in centromeric chromatin remodeling. Affinity purification/mass spectrometry of CENP-A nucleosome complexes Nature cell biology Medium 16622419
2008 The N-terminal peptidase homology domain of Spt16 (Spt16-N, ortholog of SUPT16H N-terminus) is a binding module for histones H3-H4; crystal structure at 2.1 Å reveals an aminopeptidase P fold that has lost catalytic activity but directly binds H3-H4 globular core domains and N-terminal tails through distinct surfaces; mutations in a conserved surface pocket or H4 tail modification reduce interaction. X-ray crystallography (2.1 Å), in vitro binding assays, site-directed mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 18579787
2008 Histone H2A monoubiquitination prevents FACT recruitment at transcriptional promoter regions, thereby blocking RNA polymerase II release at the early stage of elongation, identifying H2A ubiquitination as a mechanism that antagonizes SUPT16H/FACT function. ChIP, RNA interference knockdown, in vitro transcription assays Molecular cell Medium 18206970
2009 FACT (SUPT16H-containing complex) and Asf1 are each required for nucleosome disassembly at distinct regions of the yeast HO promoter; FACT and Asf1 bind upstream promoter elements before gene activation and are required for sequential re-recruitment of Swi/Snf, SAGA, and Mediator coactivators. Chromatin immunoprecipitation (ChIP), genetic mutant analysis, cell-cycle-resolved chromatin analysis in yeast Molecular cell Medium 19481521
2009 In contrast to its role in assembling chromatin within open reading frames, yeast FACT (Spt16-containing) is involved in disassembly of histones H2A/H2B from the PHO5 promoter during transcriptional induction; FACT acts at the promoter level to facilitate chromatin disassembly and transcriptional initiation. Genetic mutant analysis, chromatin immunoprecipitation in yeast The Journal of biological chemistry Medium 19574230
2011 SUPT16H (FACT component) is required for DNA double-strand break (DSB) repair: SUPT16H knockdown causes sustained γH2AX phosphorylation, decreased H3K56 acetylation, impaired cell cycle checkpoint activation, and defective DNA end resection. RNF40-mediated H2B ubiquitination promotes FACT recruitment to chromatin following DSB induction, and both RNF40 and SUPT16H cooperate to enable proper chromatin dynamics for timely DNA repair. siRNA knockdown, γH2AX immunofluorescence, H3K56ac and ChIP assays, DNA repair functional assays Cell cycle Medium 22031019
2013 SUPT16H (FACT) directly binds RNF20 in vivo and is required for RNF20 recruitment to DNA double-strand break sites; depletion of SUPT16H causes defects in RNF20-mediated H2B ubiquitylation, impaired accumulation of SNF2h, and pronounced defects in RAD51 and BRCA1 recruitment, demonstrating FACT's primary role in initiating homologous recombination repair by enabling chromatin remodeling. Co-IP, siRNA knockdown, immunofluorescence at DSB sites, HR activity assays, epistasis with nucleosome relaxation Journal of cell science Medium 24357716
2017 FACT (SSRP1 subunit) binds rapidly to genomic regions undergoing B-to-Z DNA transition induced by curaxin drug or negative supercoiling; purified SSRP1 and its isolated CID domain bind Z-form DNA or methylated alternating purine/pyrimidine sequences more strongly than other DNA types; FACT binding to alternative DNA structures triggers a p53 response, identifying FACT as a sensor of DNA torsional stress. In vitro DNA binding assays with purified proteins, ChIP in curaxin-treated cells, p53 reporter assays Nucleic acids research Medium 28082391
2018 FACT (SUPT16H-containing complex) maintains cell identity and acts as a barrier to transcription factor-mediated cell fate reprogramming in both C. elegans and human fibroblasts; FACT depletion enhances reprogramming efficiency and is associated with increased expression of FACT-occupied reprogramming-promoting genes, revealing an unexpected repressive function of FACT at specific loci. C. elegans genetic screen, siRNA depletion in human fibroblasts, RNA-seq, ChIP-seq Developmental cell Medium 30078731
2019 FACT stimulates Ubp10 deubiquitinase activity on nucleosomes (but not on other substrates), and FACT mutant strains show elevated H2B-Ub levels in vivo; FACT and Ubp10 (but not Ubp8) genetically interact to coordinate nucleosome assembly during DNA replication and transcription, revealing a functional connection between SUPT16H/FACT and H2B deubiquitination. In vitro deubiquitination assays with nucleosome substrates, yeast genetic interaction analysis, H2B-Ub level measurement eLife Medium 30681413
2019 OTUD5 deubiquitinase co-localizes and directly interacts with FACT component SPT16 (SUPT16H) at DNA double-strand breaks, independently of its interaction with UBR5; both the scaffolding (FACT-binding) and catalytic (UBR5-stabilizing) activities of OTUD5 are required for arresting RNA Pol II elongation at DNA lesions, defining FACT as a regulator of transcription at damaged chromatin. DUB RNAi screen, Co-IP, DSB localization (laser micro-irradiation), RNA synthesis assays, H2A deposition assays Nucleic acids research Medium 30508113
2021 Cryo-EM structures of transcribing yeast Pol II-Spt4/5-nucleosome complexes reveal that Pol II progression through a nucleosome activates Chd1, enables FACT binding to the partially unraveled nucleosome (excluding Chd1 and Spt5), and triggers FACT-mediated histone transfer to upstream DNA; FACT binding to the partially unraveled nucleosome requires Spt4/5 and TFIIS. Cryo-EM structure determination, in vitro reconstituted chromatin transcription assays Nature structural & molecular biology High 33846633
2021 In fission yeast, FACT recruitment to heterochromatin occurs via two distinct mechanisms: (1) Pob3 mediates Spt16 recruitment through its dimerization and tandem PH domains, and (2) HP1/Swi6 mediates Spt16 recruitment through physical interaction of the Swi6 chromo-shadow domain (CSD) charged loop with Spt16 peptidase-like domains; loss of both pathways causes severe H3K9 methylation defects and HP1/Swi6 mislocalization. ChIP, co-IP, CSD point mutant analysis, genetic silencing assays in fission yeast Cell reports Medium 34407404
2022 FACT (SUPT16H/SSRP1) physically interacts with transcription factors TFEB and TFE3 upon nuclear translocation induced by nutrient deprivation or oxidative stress; FACT depletion or inhibition (curaxin) severely impairs induction of antioxidant and lysosomal genes without affecting TFEB activation or promoter binding, identifying FACT-mediated nucleosome remodeling at stress-responsive gene promoters as essential for efficient TFEB/TFE3 transcriptional output. Co-IP, siRNA knockdown, curaxin inhibitor treatment, RT-qPCR, luciferase reporter assays Autophagy Medium 35230915
2022 The fork protection complex subunit Tof1 recruits FACT to the replication fork via interaction with the N-terminal region of Spt16; nucleosome reorganization by FACT requires coordinated engagement by the middle and C-terminal domains of Spt16 and Pob3 (not the N-terminus); these interactions are essential for robust in vitro chromatin replication. Single-molecule FRET, structure-guided pulldowns, in vitro chromatin replication assays Nucleic acids research High 35061899
2022 Glycolytic metabolite pyruvate produced by PKM2 (phosphorylated at S222 upon DNA damage) directly binds SSRP1 subunit of FACT; this interaction increases FACT complex association with γH2AX and facilitates FACT-mediated chromatin loading of γH2AX, promoting DNA repair and radiation resistance in glioblastoma cells. Co-IP, in vitro binding assays, mass spectrometry, siRNA knockdown, irradiation survival assays Advanced science Medium 35048565
2024 Rapid depletion of FACT (SUPT16H-containing) from human cells destabilizes chromatin, impairs promoter-proximal RNA Pol II pausing and elongation, and increases premature termination; the +1 nucleosome maintained by FACT is required for promoter-proximal pausing independently of NELF, establishing FACT as an in vivo regulator of chromatin architecture and Pol II pausing. Rapid protein depletion (degron), multi-omics (ChIP-seq, PRO-seq, RNA-seq) after acute FACT depletion in human cells Molecular cell High 38810649

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2003 FACT facilitates transcription-dependent nucleosome alteration. Science (New York, N.Y.) 695 12934006
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 The human CENP-A centromeric nucleosome-associated complex. Nature cell biology 593 16622419
2006 Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell 590 16713563
1998 FACT, a factor that facilitates transcript elongation through nucleosomes. Cell 546 9489704
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2004 Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Molecular cell 495 15546612
1999 The chromatin-specific transcription elongation factor FACT comprises human SPT16 and SSRP1 proteins. Nature 459 10421373
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2013 The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. The Journal of biological chemistry 413 23463506
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2015 Aerobic glycolysis tunes YAP/TAZ transcriptional activity. The EMBO journal 362 25796446
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2008 Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase II transcriptional elongation. Molecular cell 307 18206970
2006 Reversal of hepatic fibrosis -- fact or fantasy? Hepatology (Baltimore, Md.) 302 16447275
2009 Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler. Proceedings of the National Academy of Sciences of the United States of America 300 19666485
1998 Bone tunnel enlargement after anterior cruciate ligament reconstruction: fact or fiction? Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 278 9826805
2011 NG2-glia as multipotent neural stem cells: fact or fantasy? Neuron 232 21609823
2018 The proton sponge hypothesis: Fable or fact? European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 225 29859281
1989 Anticipation in myotonic dystrophy: fact or fiction? Brain : a journal of neurology 216 2731029
2003 Adult stem cell plasticity: fact or artifact? Annual review of cell and developmental biology 190 14570561
2011 The histone chaperone FACT: structural insights and mechanisms for nucleosome reorganization. The Journal of biological chemistry 179 21454601
2021 Diabetes Fact Sheets in Korea, 2020: An Appraisal of Current Status. Diabetes & metabolism journal 170 33434426
1991 Mutations in SPT16/CDC68 suppress cis- and trans-acting mutations that affect promoter function in Saccharomyces cerevisiae. Molecular and cellular biology 146 1922073
2022 Bystander effect of antibody-drug conjugates: fact or fiction? Current oncology reports 129 35305211
2002 Intermittent hypoxic training: fact and fancy. High altitude medicine & biology 128 12162862
1999 The AT2 receptor: fact, fancy and fantasy. Regulatory peptides 123 10395404
2017 "Mesenchymal stem cells": fact or fiction, and implications in their therapeutic use. F1000Research 121 28491279
1979 Inhibin--fact or artifact. Molecular and cellular endocrinology 121 376371
2011 Opioid receptor subtypes: fact or artifact? British journal of anaesthesia 117 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
2003 Oxidative stress in cardiovascular disease: myth or fact? Archives of biochemistry and biophysics 113 14654060
2021 Structural basis of nucleosome transcription mediated by Chd1 and FACT. Nature structural & molecular biology 108 33846633
2020 The role of FACT in managing chromatin: disruption, assembly, or repair? Nucleic acids research 107 33104782
2005 MDR1 genotype-related pharmacokinetics: fact or fiction? Drug metabolism and pharmacokinetics 106 16415525
2001 Exercise-induced muscle damage and inflammation: fact or fiction? Acta physiologica Scandinavica 99 11412135
1999 Psychoneuroimmunology and cancer: fact or fiction? European journal of cancer (Oxford, England : 1990) 96 10673969
2021 Antiaging diets: Separating fact from fiction. Science (New York, N.Y.) 95 34793210
2018 Structure and function of the histone chaperone FACT - Resolving FACTual issues. Biochimica et biophysica acta. Gene regulatory mechanisms 94 30055319
2000 Adverse effects of creatine supplementation: fact or fiction? Sports medicine (Auckland, N.Z.) 93 10999421
2009 FACT and Asf1 regulate nucleosome dynamics and coactivator binding at the HO promoter. Molecular cell 92 19481521
2006 Production of interferon-gamma by myeloid cells--fact or fancy? Trends in immunology 88 16698319
1997 Nitric oxide, the biological mediator of the decade: fact or fiction? The European respiratory journal 85 9073009
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 80 28082391
2011 Antioxidant therapy in male infertility: fact or fiction? Asian journal of andrology 75 21516118
2009 Auxin signaling in algal lineages: fact or myth? Trends in plant science 75 19285905
2005 Tumor counterattack: fact or fiction? Cancer immunology, immunotherapy : CII 72 15889255
2005 Geologically ancient DNA: fact or artefact? Trends in microbiology 71 15866038
2005 Mycoplasma host specificity: fact or fiction? Veterinary journal (London, England : 1997) 66 16266844
2018 FACT Sets a Barrier for Cell Fate Reprogramming in Caenorhabditis elegans and Human Cells. Developmental cell 65 30078731
1997 The M5 (m5) receptor subtype: fact or fiction? Life sciences 65 9121354
2019 Sulfonamide Hypersensitivity: Fact and Fiction. The journal of allergy and clinical immunology. In practice 64 31495421
2014 Helicobacter pylori infection and diabetes: is it a myth or fact? World journal of gastroenterology 64 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.) 64 22031019
2005 Indeterminate cell histiocytosis: fact or fiction? Journal of cutaneous pathology 61 16115054
2019 The OTUD5-UBR5 complex regulates FACT-mediated transcription at damaged chromatin. Nucleic acids research 60 30508113
2011 Quasispecies as a matter of fact: viruses and beyond. Virus research 60 21945638
2022 Human age reversal: Fact or fiction? Aging cell 58 35778957
2007 Cell membrane reactivity of MIB-1 antibody to Ki67 in human tumors: fact or artifact? Applied immunohistochemistry & molecular morphology : AIMM 57 17525638
2006 Recovery plateau following stroke: fact or fiction? Disability and rehabilitation 57 16777768
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
2009 FACT and the proteasome promote promoter chromatin disassembly and transcriptional initiation. The Journal of biological chemistry 54 19574230
2013 Histone chaperone FACT regulates homologous recombination by chromatin remodeling through interaction with RNF20. Journal of cell science 51 24357716
2015 Interaction between periodontal disease and atherosclerotic vascular disease--Fact or fiction? Atherosclerosis 50 26100678
2012 Renal stem cells: fact or science fiction? The Biochemical journal 49 22574774
1978 Glutathione peroxidase: fact and fiction. Ciba Foundation symposium 49 383423
1980 High affinity binding of tricyclic antidepressants to histamine H1-receptors: fact and artifact. European journal of pharmacology 47 6106553
1999 Nongenomic steroid actions: fact or fantasy? Vitamins and hormones 46 10232053
1985 Regeneration of endoderm from primitive ectoderm in the mouse embryo: fact or artifact? Journal of embryology and experimental morphology 46 4078535
2010 Policosanols as nutraceuticals: fact or fiction. Critical reviews in food science and nutrition 45 20301014
2015 Prevention of vasculopathy by vitamin K supplementation: can we turn fiction into fact? Atherosclerosis 43 25744701
2014 Human gamma delta T regulatory cells in cancer: fact or fiction? Frontiers in immunology 43 25477885
2013 The role of FACT in making and breaking nucleosomes. Biochimica et biophysica acta 43 24459727
2017 N,N-dimethyltryptamine and the pineal gland: Separating fact from myth. Journal of psychopharmacology (Oxford, England) 42 29095071
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
2005 Hairy cell leukemia variant: fact or fiction. American journal of clinical pathology 41 15762289
1999 Vaccines and diagnostic methods for bovine mastitis: fact and fiction. Advances in veterinary medicine 41 9890021
2012 Is belief larger than fact: expectations, optimism and reality for translational stem cell research. BMC medicine 39 23131007
2022 The fork protection complex recruits FACT to reorganize nucleosomes during replication. Nucleic acids research 38 35061899
1998 The euryarchaeotes, a subdomain of Archaea, survive on a single DNA polymerase: fact or farce? Genes & genetic systems 38 10333564
2022 Pyruvate Facilitates FACT-Mediated γH2AX Loading to Chromatin and Promotes the Radiation Resistance of Glioblastoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 37 35048565
2015 Dysplastic nevus: Fact and fiction. Journal of the American Academy of Dermatology 36 26037217
2012 The methodology of negative pressure wound therapy: separating fact from fiction. Journal of plastic, reconstructive & aesthetic surgery : JPRAS 36 22236476
2023 Declining Risk of Sudden Cardiac Death in Heart Failure: Fact or Myth? Circulation 34 36848410
2014 The role of stem cells in aesthetic surgery: fact or fiction? Plastic and reconstructive surgery 34 24732654
2019 FACT and Ubp10 collaborate to modulate H2B deubiquitination and nucleosome dynamics. eLife 33 30681413
2019 HDL: Fact, fiction, or function? HDL cholesterol and cardiovascular risk. European journal of preventive cardiology 33 33838035
2006 Gene therapy for erectile dysfunction: fact or fiction? European urology 32 16950560
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
2012 Peripheral modulation of smell: fact or fiction? Seminars in cell & developmental biology 29 22986099
2000 Aggressive basal cell carcinoma in young patients: fact or fiction? British journal of plastic surgery 29 10876275
2024 FACT maintains chromatin architecture and thereby stimulates RNA polymerase II pausing during transcription in vivo. Molecular cell 28 38810649
2013 Fact or fiction--identifying the elusive multiple myeloma stem cell. Journal of hematology & oncology 28 24314019
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1976 Transformation of epithelioma adenoides cysticum into multiple rodent ulcers: fact or fallacy. A historical vignette. The British journal of dermatology 25 788764
2013 Multiple ITS haplotypes in the genome of the lichenized basidiomycete Cora inversa (Hygrophoraceae): fact or artifact? Journal of molecular evolution 23 24343640
2008 Proteolytic enzyme therapy in evidence-based complementary oncology: fact or fiction? Integrative cancer therapies 23 19116226
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