Affinage

SUPT4H1

Transcription elongation factor SPT4 · UniProt P63272

Length
117 aa
Mass
13.2 kDa
Annotated
2026-06-10
58 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUPT4H1 (human Spt4) is the small obligate subunit of the DSIF transcription elongation complex, which it forms with Spt5/SUPT5H to associate with RNA polymerase II and govern its processivity (PMID:9450929, PMID:9450930). SUPT4H1 has no free pool in cells: it binds Spt5 through a central region (distinct from its zinc finger) that is necessary and sufficient for complex formation and for DSIF-mediated transcriptional repression and activation in vitro, and depletion of either subunit destabilizes the other (PMID:12653964, PMID:33333262). Structural and single-molecule work across archaeal and eukaryotic systems shows that Spt4/5 docks on the RNAP clamp coiled-coil via the Spt5 NGN domain, encloses the transcription bubble, and stabilizes the closed-clamp conformation to lock nucleic acids and enhance processivity, while competing with the initiation factor TFIIE/TFE for overlapping clamp sites during the initiation-to-elongation transition (PMID:19000817, PMID:21187417, PMID:21777815, PMID:26979960). Functionally, the complex suppresses polymerase arrest at nucleosomal and other barriers, repositioning RNAPII through gene-body nucleosomes in vivo, and acts as a general elongation factor required for transcription of essentially all genes and of long/GC-rich and repetitive sequences (PMID:26945063, PMID:28379497, PMID:34592154, PMID:30605685). It serves as a co-transcriptional recruitment platform, tethering the mRNA-localization factor She2p and the Paf1 complex (via the Spt5 CTR) to elongating polymerase (PMID:20713510, PMID:23775116), and extends to RNA Pol I elongation through G-rich rDNA (PMID:33809333). Its selective requirement for transcription through expanded trinucleotide (CAG) and hexanucleotide (C9orf72 GGGGCC) repeats makes SUPT4H1 a therapeutic target in repeat-expansion neurodegeneration, with knockdown lowering mutant huntingtin and C9orf72 repeat products in cells and animal models (PMID:22341442, PMID:25760041, PMID:27516603). Biallelic SUPT4H1 loss-of-function variants cause a multisystem human neurodevelopmental disorder (PMID:41842694).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 Medium

    Establishing the core protein: defining yeast SPT4 as a small zinc-binding protein with a transcription (Spt-) phenotype set the genetic foundation for the factor's role in gene expression.

    Evidence Gene cloning, null mutant and cysteine mutagenesis with phenotypic analysis in S. cerevisiae

    PMID:8483459

    Open questions at the time
    • No biochemical activity assigned
    • Role of the zinc motif vs. Spt5 binding not yet distinguished
  2. 1996 Medium

    Cross-species conservation: showing the human ortholog functionally replaces yeast Spt4 established SUPT4H1 as a true functional ortholog and a nuclear protein.

    Evidence cDNA cloning, yeast complementation, subcellular fractionation

    PMID:8649394

    Open questions at the time
    • No human-specific partners or substrates defined
    • Mechanism of action not addressed
  3. 1998 High

    Defining the complex and its target: identifying SUPT4H1 as a DSIF subunit with Spt5 that binds RNA Pol II and controls processivity answered what molecular machine Spt4 belongs to and what it regulates.

    Evidence Biochemical purification, in vitro transcription, reconstitution (human) and Co-IP plus genetic epistasis (yeast)

    PMID:9450929 PMID:9450930

    Open questions at the time
    • Structural basis of complex and Pol II contact unknown
    • Dual pausing/elongation-stimulation roles not mechanistically reconciled
  4. 2003 Medium

    Mapping the interaction interface: showing the central region (not the zinc finger) of hSpt4 binds Spt5 and that no free hSpt4 exists defined the obligate heterodimer architecture.

    Evidence Immunodepletion, in vitro transcription with deletion/point mutants from HeLa extracts

    PMID:12653964

    Open questions at the time
    • Atomic structure of the interface not yet resolved
    • Function of the zinc finger left unexplained
  5. 2003 High

    Linking to elongation through difficult templates: demonstrating Spt4 requirement for long/GC-rich transcription and synthetic interactions with THO placed Spt4/5 at a discrete step of mRNA biogenesis.

    Evidence In vitro elongation assay and yeast genetics (lethality, recombination)

    PMID:12554661

    Open questions at the time
    • Molecular basis of template-length selectivity unknown
    • Relationship to repeat sequences not yet explored
  6. 2008 High

    Structural definition of the heterodimer: the Spt4–Spt5 NGN crystal structure revealed an acid-dipole interface governing complex assembly, conserved into archaea.

    Evidence X-ray crystallography plus mutagenesis (yeast and archaeal)

    PMID:19000817

    Open questions at the time
    • How the heterodimer engages RNAP not yet shown
    • Functional consequence of interface mutation in vivo limited
  7. 2011 High

    Mechanism of processivity: structures and FRET showed Spt5 NGN docks on the RNAP clamp coiled-coil, closes the clamp around nucleic acids, and competes with TFE/TFIIE for the same site, explaining the initiation-to-elongation switch.

    Evidence X-ray crystallography, cryo-EM, single-molecule FRET in archaeal/RNAP systems

    PMID:20197319 PMID:21187417 PMID:21386817 PMID:21777815

    Open questions at the time
    • Eukaryote-specific contributions of KOW/CTR regions not captured
    • Dynamics in a native chromatin context unresolved
  8. 2016 High

    Anti-arrest activity and conformational basis: in vitro and single-molecule work established that Spt4/5 stabilizes the closed clamp and suppresses RNAPII arrest via NGN contacts with the non-template strand.

    Evidence In vitro RNAPII arrest assays, crosslinking, mutagenesis, single-molecule FRET

    PMID:26945063 PMID:26979960

    Open questions at the time
    • Quantitative contribution in cells not measured
    • Role of the nascent transcript requirement not fully defined
  9. 2017 High

    Anti-pausing through nucleosomes: showing Spt4/5 suppresses RNAPII pausing at the H3/H4 arrest point and stabilizes a partially unwrapped nucleosomal intermediate connected elongation control to chromatin.

    Evidence In vitro transcription through reconstituted nucleosomes plus single-molecule FRET

    PMID:28379497

    Open questions at the time
    • In vivo generality across nucleosome positions then untested
    • Cooperation with chromatin remodelers unknown
  10. 2013 Medium

    Co-transcriptional recruitment platform: defining direct Spt5-CTR/Rtf1 and Spt4/5/She2p interactions showed how the elongation complex couples transcription to Paf1C recruitment and mRNA localization.

    Evidence In vitro binding, Co-IP, ChIP, live imaging in yeast

    PMID:20713510 PMID:23775116

    Open questions at the time
    • Direct contribution of SUPT4H1 (vs Spt5) to recruitment not separately quantified
    • Generality beyond ASH1/active chromatin unclear
  11. 2016 High

    Repeat-selective transcription and therapeutic rationale: cross-species work established that Spt4/SUPT4H1 is selectively required for transcription through expanded CAG and C9orf72 repeats, and its reduction lowers toxic repeat products.

    Evidence Yeast genetic screen, RNA-seq, mammalian siRNA, in vivo ASO and heterozygous deletion in HD mice, patient-cell knockdown for C9orf72

    PMID:22341442 PMID:25760041 PMID:27516603

    Open questions at the time
    • Molecular basis of repeat selectivity at the polymerase level incomplete
    • Therapeutic window vs. general transcription role not resolved
  12. 2019 Medium

    General vs. selective role: global RNA reduction upon SUPT4H1 depletion established that the complex is a general elongation factor, qualifying the repeat-selective interpretation.

    Evidence RNAi in human cells with global RNA quantification and transcriptome analysis

    PMID:30605685

    Open questions at the time
    • Degree of partial knockdown selectivity for repeats not reconciled
    • Cell-type and dosage dependence unaddressed
  13. 2021 High

    In vivo elongation and Pol I roles: genome-wide work showed Spt4 promotes RNAPII movement through gene-body nucleosomes and supports Pol I processivity through G-rich rDNA, broadening its scope beyond Pol II.

    Evidence NET-seq, MNase-seq, ChIP-seq in spt4Δ yeast

    PMID:33809333 PMID:34592154

    Open questions at the time
    • Whether Pol I role is conserved in humans untested
    • Mechanistic link between nucleosome spacing changes and elongation defects partial
  14. 2026 Medium

    Human disease link: identifying biallelic SUPT4H1 loss-of-function variants causing a multisystem neurodevelopmental disorder established a direct Mendelian role for the gene.

    Evidence Exome/genome sequencing, C. elegans functional modeling, patient-fibroblast multiomics

    PMID:41842694

    Open questions at the time
    • Single study not independently replicated
    • Mechanistic connection between elongation defect and developmental phenotype incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SUPT4H1's general elongation function is reconciled with selective dependence of repeat-expansion transcripts and with tissue-specific neurodevelopmental requirements remains unresolved.
  • No structure of the human DSIF–Pol II complex on a repeat template
  • Determinants of repeat-length selectivity at atomic resolution unknown
  • Distinct contributions of SUPT4H1 vs SUPT5H to disease phenotypes undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0045182 translation regulator activity 4 GO:0140110 transcription regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0003723 RNA binding 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3
Partners
ELF1RPB1RTF1SHE2PSUPT5H
Complex memberships
DSIF (SUPT4H1–SUPT5H/Spt4–Spt5)

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Human SUPT4H1 (Spt4/hSpt4) is a subunit of DSIF (DRB sensitivity-inducing factor), a two-subunit complex with Spt5/p160 that associates with RNA polymerase II and regulates its processivity: DSIF causes DRB/H8-dependent pausing of Pol II and can also stimulate elongation rate at limiting NTP concentrations. Biochemical purification from HeLa nuclear extracts, in vitro transcription assays, recombinant protein reconstitution, cDNA cloning Genes & development High 9450929
1998 Yeast Spt4 and Spt5 form a tight complex (without Spt6) that physically associates with RNA Pol II in vivo and is required for normal transcription elongation; spt4/spt5 mutants show elongation defects and genetic suppression by RNA Pol II largest-subunit mutations. Co-immunoprecipitation, genetic epistasis (allele-specific suppression of spt5 by RNA Pol II mutations), in vivo phenotypic analysis Genes & development High 9450930
1993 Yeast SPT4 encodes a 102-amino-acid protein with a zinc-binding motif (four cysteines); mutational analysis shows at least some cysteines are essential for SPT4 function; spt4 null mutants are viable with an Spt- transcription phenotype. Gene cloning, sequencing, null mutant construction, cysteine mutagenesis, phenotypic analysis Molecular & general genetics Medium 8483459
1996 Human SUPT4H1 encodes a nuclear protein 42% identical to yeast Spt4p that functionally complements all yeast spt4 mutant phenotypes when expressed in S. cerevisiae, establishing it as a true functional ortholog. cDNA cloning, yeast complementation assay, nuclear localization by subcellular fractionation/expression analysis Molecular and cellular biology Medium 8649394
2000 Deletion of SPT4 suppresses the transcription-coupled nucleotide excision repair (TCR) defect of rad26 mutants by reactivating TCR in a Rad26-independent manner, indicating that Spt4-mediated elongation regulation modulates TCR competence of RNA Pol II. Yeast genetics (double mutant analysis), UV sensitivity assays, TCR assay The EMBO journal Medium 11101522
2001 Spt4-Spt5 genetically interacts with the Pol II CTD and CTD-modifying kinases (Kin28, Bur1, Ctk1) and phosphatase (Fcp1); Spt5 co-immunoprecipitates with both hyper- and hypophosphorylated Pol II CTD, and CTD mutations do not prevent Spt5-Pol II binding. Yeast genetic interaction analysis (synthetic phenotypes), co-immunoprecipitation Genetics Medium 11606527
2002 Spt4 mediates loss of Ser5-phosphorylated RNA Pol II at active genes in response to UV DNA damage; in spt4-null cells, this loss is suppressed even under persistent damage, demonstrating a direct role for Spt4 in transcription shutdown after DNA damage. ChIP (chromatin immunoprecipitation) with anti-phospho-Pol II antibodies, yeast genetics Nucleic acids research Medium 12177294
2003 In vitro structure-function analysis of human Spt4: immunodepletion of hSpt5 co-depletes hSpt4, indicating no free hSpt4 exists in cells; the central region (not the zinc finger) of hSpt4 is necessary and sufficient for hSpt5 binding and for DSIF-mediated transcriptional repression and activation in vitro. Immunodepletion from HeLa nuclear extracts, in vitro transcription with Spt4 deletion/point mutants, co-depletion assay Genes to cells Medium 12653964
2003 Yeast Spt4 is required for transcription elongation of long/GC-rich sequences (including lacZ) in vivo and in a novel in vitro elongation assay; spt4Δ shows synthetic lethality with THO complex mutants and hyper-recombination, placing Spt4-Spt5 and THO at different steps of mRNA biogenesis. In vitro transcription elongation assay, yeast genetics (double mutant lethality, recombination assay), gene expression analysis The EMBO journal High 12554661
2008 Crystal structure of yeast Spt4 bound to the NGN domain of Spt5 reveals that Spt4-Spt5 binding is governed by an acid-dipole interaction; mutations disrupting this interface disrupt the complex; archaeal Spt4 and Spt5 homologs also form a complex via conserved residues. X-ray crystallography, mutagenesis, biochemical complex formation assay Structure High 19000817
2010 Crystal structure of archaeal (M. jannaschii) Spt4/5 complex; the Spt5 NGN domain is the effector domain that mediates RNAP interaction and is essential for elongation stimulation; a hydrophobic pocket on Spt5 NGN binds RNAP; the RNAP clamp coiled-coil is the binding site for Spt4/5. X-ray crystallography, domain deletion analysis, mutagenesis, in vitro transcription in recombinant archaeal system Nucleic acids research High 20197319
2010 Crystal structure and cryo-EM reconstruction of the RNAP–Spt4/5 complex show that Spt4/5 binds in the middle of the RNAP clamp, encloses DNA in the transcription bubble, and contacts the non-template strand upstream of RNAP, acting as an upstream DNA holder to enhance processivity. X-ray crystallography, cryo-electron microscopy, single-particle analysis Proceedings of the National Academy of Sciences High 21187417
2011 Crystal structure of archaeal Spt4/5 bound to the RNAP clamp domain; the Spt5 NGN domain closes the RNAP active-centre cleft to lock nucleic acids and render the elongation complex processive; the KOW1 domain is mobile and positioned near the RNA exit tunnel. X-ray crystallography, structural modelling of complexes from all kingdoms The EMBO journal High 21386817
2011 TFE (TFIIE archaeal homolog) and Spt4/5 compete for overlapping binding sites on the RNAP clamp; Spt4/5 represses promoter-directed transcription in the absence of TFE; TFE displaces Spt4/5 during initiation; during elongation, Spt4/5 displaces TFE and stimulates processivity. Single-molecule FRET with fluorescently labeled recombinant RNAP system, in vitro transcription competition assay Molecular cell High 21777815
2010 She2p (mRNA localization factor) is recruited cotranscriptionally to nascent bud-localized mRNAs via direct interaction with the RNA Pol II elongation machinery through Spt4-Spt5; mutations in SPT4 or SPT5 reduce cotranscriptional She2p recruitment at ASH1 gene and disrupt ASH1 mRNA localization to the bud tip. Co-immunoprecipitation, ChIP, live-cell fluorescence microscopy, genetic analysis (spt4/spt5 mutants) Genes & development High 20713510
2012 Yeast Spt4 is selectively required for transcription through long trinucleotide (CAG) repeats; spt4 mutation selectively decreases synthesis of expanded polyQ protein without affecting normal proteins; inhibition of mammalian Supt4h reduces mutant huntingtin protein in neuronal cells and decreases aggregation and toxicity without altering overall cellular mRNA synthesis. Yeast genetic screen, RNA-seq, mammalian siRNA knockdown, huntingtin aggregation assay Cell High 22341442
2012 In immunoglobulin class switch recombination, Spt4 (as part of DSIF) suppresses cryptic transcription from the intronic Sμ region and is required for DNA repair via non-homologous end joining (NHEJ) and homologous recombination (HR), independently of Spt5's role in H3K4me3 regulation and DNA cleavage. siRNA knockdown in CH12F3-2A B cells, CSR assay, NHEJ/HR repair substrate assays, expression arrays, ChIP PLoS genetics Medium 22570620
2013 The Rtf1 subunit of the Paf1 complex directly interacts with the Spt5 CTR (C-terminal repeat domain); this interaction is necessary and sufficient for Paf1C recruitment to active chromatin; disruption of the Rtf1 Spt5-interacting domain or Spt5 CTR deletion releases Paf1C from chromatin. In vitro binding assay, Co-IP, ChIP, yeast genetics (mutation analysis) Molecular and cellular biology Medium 23775116
2015 Reduction of Supt4h (mouse SUPT4H1) in brains of HD model mice (zQ175, R6/2) by ASO injection or heterozygous deletion selectively decreases mRNA and protein from mutant HTT alleles with expanded CAG repeats, reduces HTT aggregation, prolongs lifespan, and delays motor impairment in R6/2 mice. In vivo ASO knockdown, genetic heterozygous deletion, behavioral testing, protein aggregation assay, qPCR/Western blot PLoS genetics High 25760041
2016 SUPT4H1 (human Spt4) knockdown selectively decreases production of both sense (GGGGCC) and antisense (GGCCCC) expanded repeat transcripts from C9orf72, as well as their translated dipeptide repeat (DPR) products, in patient-derived cells; targeting Spt4 also mitigated neurodegeneration in animal models. siRNA knockdown in patient-derived cells, RNA foci quantification, DPR protein immunoassay, animal model rescue experiments Science High 27516603
2016 Yeast Spt4/5 binds single-stranded RNA in a sequence-specific manner (preferring AAN repeats); the major RNA-binding determinants are Spt4 together with the NGN domain of Spt5, not the KOW domains. Electrophoretic mobility shift assay (EMSA), domain deletion analysis, RNA binding biochemistry Protein science Medium 27376968
2016 Spt4/5 stabilizes the RNAP clamp in the closed conformation during elongation complexes; the non-template strand and Spt4/5 each independently stimulate transcription processivity by modulating clamp dynamics; TFE opens the clamp during initiation while Spt4/5 promotes clamp closure during elongation. Single-molecule FRET with fluorescently labeled recombinant archaeal RNAP system Proceedings of the National Academy of Sciences High 26979960
2016 Spt4/5 biochemically suppresses RNAPII arrest: the eukaryotic-specific KOW-containing regions of Spt5 stabilize association with RNAPII elongation complexes (requiring the nascent transcript); charged residues in the Spt5 NGN domain contact the non-template strand and DNA in the transcription bubble, and their mutation abolishes anti-arrest activity without preventing Spt4/5 binding to elongation complexes. In vitro RNAPII elongation arrest assay, site-directed mutagenesis, DNA-protein crosslinking, domain deletion analysis Journal of Biological Chemistry High 26945063
2017 Spt4/5 is a general elongation factor in archaea, occupying essentially all transcribed genes and correlating with RNAP occupancy; on most genes Spt4/5 is recruited proximally to the transcription start site, while on rRNA and CRISPR loci it is recruited during early elongation (~500 bp from TSS). Genome-wide ChIP-seq (archaeal), RNA-seq Nature microbiology Medium 28248297
2017 Spt4/5 suppresses RNAPII pausing at the major H3/H4-induced arrest point during transcription through nucleosomes, repositions RNAPII further into the nucleosome, and stabilizes a nucleosomal intermediate with partially unwrapped DNA behind RNAPII as detected by single-molecule FRET. In vitro transcription through reconstituted nucleosomes, single-molecule FRET Nucleic acids research High 28379497
2019 SUPT4H1 depletion by RNAi leads to a global reduction in all cellular RNA (not selective for repeat-containing transcripts), indicating that SUPT4H1 is required for general transcription by the SUPT4H1/SUPT5H elongation complex. RNAi knockdown in human cells, global RNA quantification, transcriptome analysis Cell reports Medium 30605685
2019 The Spt4-Spt5 complex negatively regulates ATG genes (ATG8, ATG41) in yeast during active growth, inhibiting autophagy; under autophagy-inducing conditions, Spt5 phosphorylation releases this repression and allows upregulation of autophagy. Yeast genetic analysis, ChIP, RT-qPCR, autophagy flux assays, phosphorylation analysis Autophagy Medium 31462158
2020 Single-molecule fluorescence imaging shows that Spt4/5 binding to RNAPII elongation complexes is NTP-dependent (requires active transcription), typically follows RNAPII binding to DNA, is slowly reversible (residence time comparable to time to transcribe an average yeast gene), and correlates with mRNA binding protein Hek2 association. Multiwavelength single-molecule fluorescence microscopy, in vitro reconstituted activator-dependent yeast transcription system Proceedings of the National Academy of Sciences High 33293419
2020 CRISPRi depletion of Spt4 (alone or with Spt5) inhibits HIV transcription primarily at the step of Tat transactivation, decreasing Pol II and Cdk9 promoter occupancy; depletion of one DSIF subunit reduces protein stability of the partner subunit; DSIF depletion facilitates HIV entry into latency. CRISPRi knockdown, HIV transcription assay, ChIP, protein stability analysis Biochimica et biophysica acta. Gene regulatory mechanisms Medium 33333262
2021 Spt4/5 helps Pol II transcribe through CTG•CAG tract duplex (B-form DNA) but paradoxically inhibits Pol II bypass of CTG and CAG slip-out (non-B-form) structures; Elf1 individually and cooperatively with Spt4/5 also inhibits Pol II bypass of slip-out structures. In vitro reconstituted yeast transcription system with defined DNA templates containing CTG/CAG repeats and slip-out structures Nucleic acids research Medium 33877330
2021 In vivo, Spt4 associates with elongating RNAPII early in transcription and promotes RNAPII movement through gene-body nucleosomes, especially nucleosome +2; loss of Spt4 causes RNAPII accumulation upstream of nucleosomal dyads and increased spacing between gene-body nucleosomes. NET-seq (native elongating transcript sequencing), MNase-seq (nucleosome positioning), ChIP-seq in spt4Δ yeast Cell reports High 34592154
2021 Spt4 promotes RNA Pol I processivity and transcription elongation through G-rich regions of ribosomal DNA in vivo. Native Elongating Transcript sequencing (NET-seq) in spt4Δ yeast, global Pol I occupancy analysis Genes Medium 33809333
2023 Spt4 promotes cellular senescence by activating non-coding RNA transcription from the rDNA E-pro promoter; absence of Spt4 reduces E-pro ncRNA levels, increases rDNA stability, and extends yeast replicative lifespan in a SIR2-dependent manner; Spt4 levels increase with cell age. Yeast genetics (spt4Δ), replicative lifespan assay, qRT-PCR for ncRNA, rDNA stability assay, epistasis with SIR2 Cell reports Medium 36640349
2024 Cryo-EM structures of archaeal (P. furiosus) RNAP elongation complex with Spt4/5 show: Spt4/5 can bind apo-RNAP in a super-contracted clamp conformation independently of nucleic acids; Spt5-NGN contacts the DNA duplex to stabilize the upstream transcription bubble boundary; RNAP contracts upon EC formation or Spt4/5 engagement. Single-particle cryo-electron microscopy, in vitro transcription assays Nucleic acids research High 38709902
2024 In Drosophila, Spt4 and Spt5 (DSIF) are required for control of neural progenitor cell proliferation and for remodeling of axonal projections of specific mushroom body neurons; loss-of-function affects expression of a subset of genes controlling remodeling. Drosophila knock-out allele generation, mushroom body development analysis, transcriptomics Frontiers in cell and developmental biology Medium 39445331
2026 Biallelic SUPT4H1 loss-of-function variants (frameshift and missense) in humans cause a multisystem neurodevelopmental disorder; functional modeling in C. elegans confirmed pathogenicity through neuromotor deficits; multiomics of patient fibroblasts revealed dysregulation of developmental gene networks and disrupted RNA polymerase complexes and cell-cycle regulators. Exome/genome sequencing, C. elegans CRISPR/RNAi knockdown with neuromotor readout, transcriptomics and proteomics of patient fibroblasts Genetics in medicine Medium 41842694
2026 TFIIH categorically dissociates from RNAPII before Spt4/5 (DSIF) arrives during the initiation-to-elongation transition (mean interval ~35 seconds), demonstrating that Spt4/5 binding is not required to displace TFIIH from RNAPII. Single-molecule fluorescence microscopy with labeled yeast nuclear extracts, real-time imaging of factor dynamics bioRxivpreprint Medium 42146622

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes & development 626 9450929
1998 Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. Genes & development 393 9450930
2011 Architecture of the RNA polymerase-Spt4/5 complex and basis of universal transcription processivity. The EMBO journal 194 21386817
2010 Spt4/5 stimulates transcription elongation through the RNA polymerase clamp coiled-coil motif. Nucleic acids research 137 20197319
2010 RNA polymerase and transcription elongation factor Spt4/5 complex structure. Proceedings of the National Academy of Sciences of the United States of America 128 21187417
2011 The initiation factor TFE and the elongation factor Spt4/5 compete for the RNAP clamp during transcription initiation and elongation. Molecular cell 119 21777815
2012 The Spt4-Spt5 complex: a multi-faceted regulator of transcription elongation. Biochimica et biophysica acta 117 22982195
2016 Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts. Science (New York, N.Y.) 108 27516603
2012 Spt4 is selectively required for transcription of extended trinucleotide repeats. Cell 81 22341442
2003 Molecular evidence for a positive role of Spt4 in transcription elongation. The EMBO journal 80 12554661
2001 Genetic interactions of Spt4-Spt5 and TFIIS with the RNA polymerase II CTD and CTD modifying enzymes in Saccharomyces cerevisiae. Genetics 78 11606527
2008 Core structure of the yeast spt4-spt5 complex: a conserved module for regulation of transcription elongation. Structure (London, England : 1993) 62 19000817
2000 Spt4 modulates Rad26 requirement in transcription-coupled nucleotide excision repair. The EMBO journal 62 11101522
2020 Mechanisms of Transcription Elongation Factor DSIF (Spt4-Spt5). Journal of molecular biology 61 32987031
2009 Histone H3K4 and K36 methylation, Chd1 and Rpd3S oppose the functions of Saccharomyces cerevisiae Spt4-Spt5 in transcription. Genetics 61 19948887
2013 The recruitment of the Saccharomyces cerevisiae Paf1 complex to active genes requires a domain of Rtf1 that directly interacts with the Spt4-Spt5 complex. Molecular and cellular biology 60 23775116
2010 Cotranscriptional recruitment of She2p by RNA pol II elongation factor Spt4-Spt5/DSIF promotes mRNA localization to the yeast bud. Genes & development 60 20713510
2016 TFE and Spt4/5 open and close the RNA polymerase clamp during the transcription cycle. Proceedings of the National Academy of Sciences of the United States of America 55 26979960
1993 Molecular and genetic characterization of SPT4, a gene important for transcription initiation in Saccharomyces cerevisiae. Molecular & general genetics : MGG 55 8483459
2017 The elongation factor Spt4/5 regulates RNA polymerase II transcription through the nucleosome. Nucleic acids research 54 28379497
2016 Biochemical Analysis of Yeast Suppressor of Ty 4/5 (Spt4/5) Reveals the Importance of Nucleic Acid Interactions in the Prevention of RNA Polymerase II Arrest. The Journal of biological chemistry 52 26945063
2015 Effects on murine behavior and lifespan of selectively decreasing expression of mutant huntingtin allele by supt4h knockdown. PLoS genetics 44 25760041
2012 The DSIF subunits Spt4 and Spt5 have distinct roles at various phases of immunoglobulin class switch recombination. PLoS genetics 36 22570620
1996 Identification and analysis of a functional human homolog of the SPT4 gene of Saccharomyces cerevisiae. Molecular and cellular biology 34 8649394
1996 Differential intrachromosomal hyper-recombination phenotype of spt4 and spt6 mutants of S. cerevisiae. Current genetics 33 8660457
2020 Dynamics of RNA polymerase II and elongation factor Spt4/5 recruitment during activator-dependent transcription. Proceedings of the National Academy of Sciences of the United States of America 32 33293419
2017 A global analysis of transcription reveals two modes of Spt4/5 recruitment to archaeal RNA polymerase. Nature microbiology 31 28248297
2019 TFS and Spt4/5 accelerate transcription through archaeal histone-based chromatin. Molecular microbiology 26 30592095
2021 Spt4 facilitates the movement of RNA polymerase II through the +2 nucleosomal barrier. Cell reports 23 34592154
1996 Mutations in the SPT4, SPT5, and SPT6 genes alter transcription of a subset of histone genes in Saccharomyces cerevisiae. Genetics 22 8844144
2019 SUPT4H1 Depletion Leads to a Global Reduction in RNA. Cell reports 21 30605685
2003 Structure-function analysis of human Spt4: evidence that hSpt4 and hSpt5 exert their roles in transcriptional elongation as parts of the DSIF complex. Genes to cells : devoted to molecular & cellular mechanisms 21 12653964
2022 SUPT4H1-edited stem cell therapy rescues neuronal dysfunction in a mouse model for Huntington's disease. NPJ Regenerative medicine 19 35046408
2005 Analysis of a splice array experiment elucidates roles of chromatin elongation factor Spt4-5 in splicing. PLoS computational biology 19 16172632
1996 Isolation and characterization of the human and mouse homologues (SUPT4H and Supt4h) of the yeast SPT4 gene. Genomics 19 8786137
2019 Suppression of the yeast elongation factor Spt4 ortholog reduces expanded SCA36 GGCCUG repeat aggregation and cytotoxicity. Brain research 17 30610877
2022 The transient Spt4-Spt5 complex as an upstream regulator of non-coding RNAs during development. Nucleic acids research 15 35188560
2017 Virulence protein VirD5 of Agrobacterium tumefaciens binds to kinetochores in host cells via an interaction with Spt4. Proceedings of the National Academy of Sciences of the United States of America 15 28874565
2009 Characterization of the Schizosaccharomyces pombe Spt5-Spt4 complex. RNA (New York, N.Y.) 14 19460865
2023 Spt4 promotes cellular senescence by activating non-coding RNA transcription in ribosomal RNA gene clusters. Cell reports 12 36640349
2002 Transcription elongation factor Spt4 mediates loss of phosphorylated RNA polymerase II transcription in response to DNA damage. Nucleic acids research 12 12177294
2019 The transcription factor Spt4-Spt5 complex regulates the expression of ATG8 and ATG41. Autophagy 11 31462158
2021 Opposite roles of transcription elongation factors Spt4/5 and Elf1 in RNA polymerase II transcription through B-form versus non-B DNA structures. Nucleic acids research 10 33877330
2018 Architecture of the RNA polymerase II elongation complex: new insights into Spt4/5 and Elf1. Transcription 10 29624124
2014 Elongator and SPT4/SPT5 complexes as proxy to study RNA polymerase II transcript elongation control of plant development. Proteomics 10 24733746
2021 Spt4 Promotes Pol I Processivity and Transcription Elongation. Genes 9 33809333
2016 The yeast transcription elongation factor Spt4/5 is a sequence-specific RNA binding protein. Protein science : a publication of the Protein Society 9 27376968
2024 Structural basis of archaeal RNA polymerase transcription elongation and Spt4/5 recruitment. Nucleic acids research 6 38709902
1998 Comparison of murine Supt4h and a nearly identical expressed, processed gene: evidence of sequence conservation through gene conversion extending into the untranslated regions. Nucleic acids research 6 9776760
2020 CRISPRi-mediated depletion of Spt4 and Spt5 reveals a role for DSIF in the control of HIV latency. Biochimica et biophysica acta. Gene regulatory mechanisms 5 33333262
2016 Hot1 factor recruits co-activator Sub1 and elongation complex Spt4/5 to osmostress genes. The Biochemical journal 4 27480106
1998 Identification and functional analysis of a Kluyveromyces lactis homologue of the SPT4 gene of Saccharomyces cerevisiae. Current genetics 2 9871119
2020 Peptidyl inhibition of Spt4-Spt5: Protein-protein inhibitors for targeting the transcriptional pathway related to C9orf72 expansion repeats. Journal of cellular biochemistry 1 32628322
2014 Ubiquitin fusion constructs allow the expression and purification of multi-KOW domain complexes of the Saccharomyces cerevisiae transcription elongation factor Spt4/5. Protein expression and purification 1 24859675
2026 Biallelic SUPT4H1 variants cause a multisystem neurodevelopmental disorder associated with disrupted transcription. Genetics in medicine : official journal of the American College of Medical Genetics 0 41842694
2026 The transcription elongation factors Spt4 and Spt6 promote dermal adipocyte differentiation. Adipocyte 0 41891546
2026 Dynamics of TFIIH and Spt4/5 during the transition from transcription initiation to elongation. bioRxiv : the preprint server for biology 0 42146622
2024 The transcription elongation factors Spt4 and Spt5 control neural progenitor proliferation and are implicated in neuronal remodeling during Drosophila mushroom body development. Frontiers in cell and developmental biology 0 39445331

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