Affinage

SUPT5H

Transcription elongation factor SPT5 · UniProt O00267

Length
1087 aa
Mass
121.0 kDa
Annotated
2026-06-10
100 papers in source corpus 48 papers cited in narrative 47 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

SUPT5H/SPT5 is an essential, deeply conserved transcription elongation factor that, together with SPT4, forms the DSIF complex and governs the processivity of RNA polymerase II across the transcription cycle (PMID:9450929, PMID:1840633). SPT5 binds Pol II directly through its central NusG N-terminal homology (NGN) and KOW domains—with KOW4-5 contacting the Rpb4/7 subcomplex and Rpb1/Rpb2 clamp, KOW5 contacting nascent RNA, and KOW1 engaging upstream DNA to anchor DSIF on the elongation complex (PMID:24813444, PMID:28213523)—while SPT4 binds the NGN domain through an acid-dipole interface that maintains KOW conformation (PMID:19000817). DSIF exerts dual control over Pol II: it enforces promoter-proximal pausing (in part through KOW2-3-mediated NELF recruitment) and is also required for processive elongation, with depletion causing loss of paused Pol II and processivity defects that are most pronounced in long genes (PMID:9450929, PMID:28213523, PMID:34534457, PMID:29514850). This balance is set by phosphorylation: P-TEFb/CDK9 phosphorylates the C-terminal repeat (CTR) and the KOW4-5 linker to drive pause release, and coordinated phospho-states of the linker, CTR1, and CTR2 tune elongation speed, pausing, splicing, and termination (PMID:10757782, PMID:12904290, PMID:34534457, PMID:40250441, PMID:36206739). The phosphorylated Spt5 CTR provides a docking platform that recruits the PAF complex via Rtf1's Plus3 domain and licenses downstream histone modifications including H2B monoubiquitination and H3K4/K36 methylation (PMID:19581288, PMID:19365074, PMID:24101474, PMID:23775116); the CTR nonapeptide repeats also recruit mRNA capping enzymes through a Thr1-phosphorylation-controlled binary code (PMID:11893740, PMID:24939935, PMID:25414009). At gene 3' ends, PNUTS-PP1 dephosphorylates Spt5 to decelerate Pol II and license Xrn2-mediated torpedo termination, with Spt5 directly stimulating Xrn2 nuclease activity (PMID:31677974, PMID:39746995). SPT5 stabilizes promoter-proximal Pol II against Cullin 3/ARMC5- and VCP/p97-mediated ubiquitin-proteasomal degradation of RPB1 in a CDK9-dependent manner (PMID:34480849, PMID:39854452), suppresses divergent and antisense transcription (PMID:28366642, PMID:35325203), facilitates cotranscriptional spliceosome assembly (PMID:31289129), couples transcription to histone retention via an acidic N-terminal tail (PMID:35102600), and is required for enhancer transcription and super-enhancer-promoter contacts (PMID:32251373). SPT5 is additionally co-opted in specialized contexts including MYC-driven elongation (PMID:30928206), AID-dependent class switch recombination (PMID:20887897), and herpesvirus late gene expression (PMID:28743741), and is regulated post-translationally by PRMT1/PRMT5 arginine methylation (PMID:12718890) and CK2-family phosphorylation of its N-terminal acidic domain (PMID:35325203).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1991 High

    Established that SPT5 is an essential nuclear protein, framing it as a broadly required transcription factor rather than a gene-specific regulator.

    Evidence Null mutant lethality and immunofluorescence of an SPT5-β-galactosidase fusion in yeast

    PMID:1840633

    Open questions at the time
    • Did not define molecular function or interaction partners
    • No mechanism linking essentiality to transcription
  2. 1998 High

    Identified SPT5/SPT4 as the DSIF complex and resolved its paradoxical dual role in restraining and stimulating Pol II elongation, defining SPT5 as a core elongation factor.

    Evidence Biochemical purification from HeLa extracts with in vitro transcription assays, plus yeast co-IP and allele-specific genetic suppression by Pol II mutants

    PMID:9450929 PMID:9450930

    Open questions at the time
    • Domain basis of Pol II contact not yet mapped
    • Mechanistic switch between positive and negative roles unresolved
  3. 2000 High

    Mapped the modular domain architecture of SPT5 and identified CTR1 as a P-TEFb substrate, providing the first link between SPT5 phosphorylation and elongation control.

    Evidence Domain deletion in vitro transcription and recombinant P-TEFb phosphorylation assays; polytene/ChIP localization to elongating Pol II in Drosophila

    PMID:10757782 PMID:11040216 PMID:11040217

    Open questions at the time
    • Phosphorylation sites within CTR not defined
    • Downstream effectors of phospho-CTR unknown
  4. 2002 High

    Defined SPT5 as a stage-specific elongation factor required in late elongation to prevent premature RNA dissociation, refining when in the cycle SPT5 acts.

    Evidence In vitro three-stage HIV-1 transcription with immunodepletion and chase experiments

    PMID:11809800

    Open questions at the time
    • In vitro system may not capture chromatin context
    • Did not connect to physiological terminator architecture
  5. 2003 High

    Connected the Spt5 CTD to mRNA capping and identified arginine methylation as a regulatory input, establishing SPT5 as a hub coupling elongation to co-transcriptional RNA processing.

    Evidence Two-hybrid/in vitro binding of CTD to capping enzymes; PRMT1/PRMT5 in vitro methylation with arginine mutagenesis; CDK9 phosphorylation of CTD Thr1

    PMID:11893740 PMID:12556496 PMID:12718890 PMID:12904290

    Open questions at the time
    • Functional consequence of methylation in vivo not quantified
    • Capping-recruitment regulation by phosphorylation not yet structurally resolved
  6. 2009 High

    Demonstrated that kinase-dependent phosphorylation of the Spt5 CTR recruits the PAF complex and licenses elongation-coupled histone modifications, defining a phospho-CTR-to-chromatin signaling axis.

    Evidence Analog-sensitive Bur1 kinase chemical genetics, in vitro kinase assays on isolated elongation complexes, ChIP, and histone modification analysis

    PMID:19365074 PMID:19581288

    Open questions at the time
    • Direct CTR-PAF binding interface not resolved at this stage
    • Ordering of H2B ubiquitination relative to H3 methylation unclear
  7. 2008 High

    Provided the structural basis for SPT4-SPT5 assembly, explaining how SPT4 maintains the elongation-competent conformation of SPT5 KOW domains.

    Evidence Crystal structure of Spt4-NGN with interface mutagenesis and archaeal complex reconstitution

    PMID:19000817

    Open questions at the time
    • Did not capture SPT5 in the context of Pol II
    • KOW domain functions inferred, not directly tested
  8. 2013 High

    Defined at atomic resolution how phosphorylated Spt5 CTR is read by Rtf1/Plus3, establishing the molecular recruitment mechanism for the PAF complex.

    Evidence X-ray structure of Rtf1 Plus3 with phospho-Spt5 repeat, in vitro binding mutagenesis, and ChIP; complemented by direct Rtf1-CTR interaction mapping

    PMID:23775116 PMID:24101474

    Open questions at the time
    • Stoichiometry of multivalent CTR-PAF engagement unresolved
    • Kinase specificity setting the phospho-mark in human cells not addressed
  9. 2014 High

    Mapped SPT5-Pol II contacts at residue resolution and decoded the capping-enzyme CTD recognition code, showing how phosphorylation toggles processing factor recruitment.

    Evidence Site-specific photocrosslinking with unnatural amino acids mapping KOW4-5/Rpb contacts; crystal structures of guanylyltransferase-CTD with synthetic-lethality validation

    PMID:24813444 PMID:24939935

    Open questions at the time
    • Dynamics of contact remodeling during the cycle not captured
    • Coupling of CTD code to elongation rate not directly measured
  10. 2010 Medium

    Broadened the SPT5 functional repertoire to Pol I association, mRNA localization, and AID-dependent class switch recombination, indicating SPT5 acts as a general elongation scaffold co-opted for specialized outcomes.

    Evidence Far Western direct binding to Pol I/II subunits; co-IP linking She2p to elongating Pol II; shRNA screen plus co-IP/ChIP-seq for AID at stalled Pol II

    PMID:20713510 PMID:20887897 PMID:21467036

    Open questions at the time
    • Pol I role mechanistically distinct from elongation not detailed
    • She2p link single-lab without structural detail
  11. 2015 High

    Resolved KOW domain structures and the CTD capping code in detail, showing nucleic-acid-binding surfaces and Thr1 phosphorylation as a binary off-switch for capping enzyme recruitment.

    Evidence Crystal structures of KOW1-Linker1/KOW2-3 and of Pct1-CTD with binding/competition assays; phospho-site mutagenesis linking CTD Thr1 to H3K4 methylation

    PMID:25414009 PMID:26217010 PMID:26275777

    Open questions at the time
    • Redundancy between KOW1 PCP and Spt4 not fully quantified in vivo
    • Whether the human CTR uses an identical code not established here
  12. 2017 High

    Genome-wide depletion studies established SPT5 as required to overcome a 5'-proximal elongation barrier and to suppress pervasive antisense transcription, defining its role in transcription directionality and progression.

    Evidence Auxin-inducible degron depletion in S. pombe with ChIP-seq, RNA-seq, NET-seq, MNase-seq; in vitro reconstituted pausing with KOW domain mutants assigning NELF recruitment and nascent-RNA contacts

    PMID:28213523 PMID:28366642

    Open questions at the time
    • Barrier composition not molecularly defined
    • How SPT5 distinguishes sense from antisense initiation unclear
  13. 2019 High

    Defined SPT5 dephosphorylation as the trigger for Pol II deceleration and torpedo termination, and quantified SPT5's contribution to elongation processivity in long genes.

    Evidence Genome-wide elongation-rate measurement with PNUTS-PP1 separation-of-function mutation; auxin-degron depletion in MEFs with elongation rate mapping; MYC-SPT5 transfer mechanism by MS/Co-IP/ChIP-seq

    PMID:29514850 PMID:30928206 PMID:31677974

    Open questions at the time
    • Phosphatase site specificity on Spt5 not fully resolved
    • MYC sequestration model not extended to other oncogenic contexts
  14. 2021 High

    Showed SPT5 actively protects promoter-proximal Pol II from ubiquitin-proteasomal destruction and is required for pause establishment and release, distinguishing its role from NELF.

    Evidence Auxin- and dTAG-inducible depletion with ubiquitination assays, Cullin 3/VCP/CDK9 dependency, PRO-seq/ChIP-seq/ATAC-seq, and phospho-mutant analysis of Ser666

    PMID:34480849 PMID:34534457

    Open questions at the time
    • E3 adaptor identity not yet defined at this stage
    • Coupling between Pol II protection and pause release mechanism incomplete
  15. 2022 High

    Refined the phospho-isoform logic of pausing versus elongation and revealed SPT5's acidic N-tail in histone retention and antisense suppression, expanding its chromatin-coupling roles.

    Evidence eNET-seq with CTR1/linker phospho-mutant rescue; cryo-EM-context analysis with histone occupancy ChIP for Spt5N; ZWC (ZC3H4/WDR82/CK2) in vitro kinase and ChIP-seq; super-enhancer 4C/Hi-C with CRISPRa rescue

    PMID:32251373 PMID:35102600 PMID:35325203 PMID:36206739

    Open questions at the time
    • Relative contribution of distinct phospho-isoforms across gene classes not unified
    • ZWC-SPT5 axis confirmed in single lab
  16. 2025 High

    Identified ARMC5 as the CUL3 adaptor for promoter-proximal Pol II degradation, dissected coordinated CTR1/CTR2/linker phospho-control, and showed SPT5 directly stimulates Xrn2 to drive termination, integrating the elongation-to-termination program.

    Evidence Proteomic screen with BTB-domain/CDK9-dependent ARMC5 validation; CRISPR phospho-mutant knock-ins in HCT116 with TT-seq/ChIP-seq; in vitro Xrn2 activity assays with Co-IP and genome-wide readouts

    PMID:39746995 PMID:39854452 PMID:40250441

    Open questions at the time
    • How phospho-marks are spatially ordered across the gene not fully resolved
    • Direct structure of SPT5-Xrn2 stimulation absent

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the full set of SPT5 phosphorylation marks, arginine methylation, and condensate/phase behavior are integrated kinetically to switch SPT5 between pausing, elongation, processing, and termination across distinct gene architectures remains unresolved.
  • No unified quantitative model linking each PTM to a defined cycle step
  • Condensate-based regulation (SEC/LEDGF) characterized only in single labs
  • Crosstalk between methylation and phosphorylation in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0005654 nucleoplasm 2 GO:0000228 nuclear chromosome 1 GO:0005634 nucleus 1
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-392499 Metabolism of proteins 2
Partners
AICDAARMC5MSL1MYCPOLR2ARTF1SUPT4H1XRN2
Complex memberships
DSIF (SPT4-SPT5)

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 DSIF, the human transcription elongation factor composed of SPT5 (p160/SUPT5H) and SPT4 (p14), was purified from HeLa nuclear extracts and shown to cause RNA polymerase II pausing in conjunction with DRB. In vitro, DSIF also stimulates elongation rate at limiting NTP concentrations, demonstrating dual positive and negative roles in Pol II processivity. Biochemical purification from HeLa extracts, in vitro transcription assay, cDNA cloning, recombinant protein complementation Genes & development High 9450929
1998 Yeast Spt5 physically associates with RNA polymerase II in vivo (co-immunoprecipitation), and genetic suppression of conditional spt5 mutations by mutations in the two largest Pol II subunits (one of which causes an elongation defect) places Spt5 in the transcription elongation machinery. Spt4 and Spt5 form a tight complex that does not contain Spt6. Co-immunoprecipitation, genetic epistasis (allele-specific suppression by Pol II mutants), conditional mutant phenotyping Genes & development High 9450930
1991 Yeast SPT5 is an essential nuclear protein; null mutation is lethal, indicating requirement for normal transcription of many genes. The protein localizes to the nucleus by indirect immunofluorescence of an SPT5-β-galactosidase fusion. Null mutant construction, indirect immunofluorescence of fusion protein, SPT5 cloning and sequencing Molecular and cellular biology High 1840633
2000 SPT5 domains required for transcriptional regulation were defined: the SPT4-binding domain, the RNA Pol II-binding domain, and the C-terminal repeat region CTR1 are all required for DRB-mediated transcriptional repression and Tat-mediated activation in vitro. The CTR1 domain is a substrate for P-TEFb (CDK9/cyclin T1) phosphorylation. Domain deletion/truncation analysis, in vitro transcription assay, phosphorylation assay with recombinant P-TEFb Molecular and cellular biology High 10757782
2000 Drosophila Spt5 colocalizes with actively elongating (phosphorylated) RNA Pol II but not with non-elongating Pol II at polytene chromosome loci, and is recruited to heat shock gene promoters before heat shock and to 5' and 3' ends of genes after heat shock induction, consistent with roles in promoter-proximal pausing and elongation. Immunofluorescence on polytene chromosomes, chromatin immunoprecipitation (ChIP) Genes & development High 11040216 11040217
2003 SPT5 is specifically methylated by protein arginine methyltransferases PRMT1 and PRMT5. Specific arginine residues in SPT5 are methylated by these enzymes, and methylation regulates SPT5 interaction with RNA polymerase II, its promoter association, and its transcriptional elongation properties. Biochemical co-association assay, in vitro methylation assay, mutagenesis of arginine residues, co-immunoprecipitation with Pol II Molecular cell High 12718890
2003 Yeast Spt5 co-immunopurifies with general elongation factors TFIIF and TFIIS, chromatin regulators Spt6 and FACT, and mRNA capping enzyme and cap methyltransferase. spt4 and spt5 mutations genetically interact with capping enzyme gene mutations and lead to accumulation of unspliced pre-mRNA, revealing roles in pre-mRNA processing. Co-immunopurification/mass spectrometry, genetic interaction analysis, pre-mRNA accumulation assay Molecular and cellular biology High 12556496
2002 Spt5 is recruited to the HIV-1 transcription complex shortly after initiation. CDK9 activation induces hyperphosphorylation of Spt5 in parallel with Pol II CTD phosphorylation. Spt5-depleted extracts show Spt5 is not required for early elongation or Tat-dependent kinase activation, but is required in late elongation to prevent premature dissociation of RNA from the transcription complex at terminator sequences and to reduce polymerase pausing at arrest sites. In vitro three-stage transcription assay, immunodepletion, chase experiments with Spt5-depleted extracts Molecular and cellular biology High 11809800
2002 Fission yeast Spt5 C-terminal domain (CTD), composed of nonapeptide repeats (TPAWNSGSK), is necessary and sufficient for binding to mRNA capping enzymes Pct1 (triphosphatase) and Pce1 (guanylyltransferase), both in two-hybrid and in vitro binding assays. Spt5 is essential in S. pombe and interacts with Spt4 via a central domain distinct from the CTD. Two-hybrid assay, in vitro binding assay with CTD truncations, genetic complementation The Journal of biological chemistry High 11893740
2009 The yeast Bur1 kinase directly phosphorylates the Spt5 C-terminal repeat domain (CTD) both in vivo and in isolated elongation complexes in vitro. Deletion of the Spt5 CTD or mutation of Spt5 serines targeted by Bur1 reduces PAF complex recruitment, decreases histone H3K4 trimethylation, and reduces Pol II CTD Ser-2 phosphorylation. Chemical genetics (analog-sensitive kinase), in vitro kinase assay with isolated elongation complexes, ChIP, histone modification analysis Molecular and cellular biology High 19581288
2009 BUR kinase phosphorylates the Spt5 CTR in vivo and in vitro, and the Spt5 CTR is required for PAF complex recruitment, histone H2B K123 monoubiquitination, and histone H3 K4/K36 trimethylation during transcription elongation. In vitro kinase assay, ChIP, histone modification western blot, genetic deletion analysis Proceedings of the National Academy of Sciences of the United States of America High 19365074
2013 Crystal structure of human Rtf1 Plus3 domain in complex with a phosphorylated Spt5 repeat reveals that Spt5 binding is mediated by a phosphothreonine recognition interface and hydrophobic contacts. Mutations disrupting this interface diminish Spt5 binding in vitro and Rtf1 chromatin localization in vivo, establishing the molecular basis for Paf1C recruitment by phosphorylated Spt5. X-ray crystallography, in vitro binding assay, ChIP (chromatin localization) Proceedings of the National Academy of Sciences of the United States of America High 24101474
2008 Crystal structure of yeast Spt4 bound to the NGN domain of Spt5 reveals an acid-dipole interaction governing Spt4-Spt5 binding. Mutations disrupting this interaction disrupt the complex. The archaeal Spt4-Spt5 homologs also form a complex, and Spt4 is positioned to maintain the functional conformation of KOW domains in Spt5. X-ray crystallography, mutagenesis of interface residues, archaeal complex reconstitution Structure High 19000817
2019 PNUTS-PP1 phosphatase dephosphorylates Spt5 downstream of poly(A) sites, causing RNA Pol II deceleration from >2 kb/min to <1 kb/min. This deceleration is required for transcription termination by allowing Xrn2 to catch and torpedo Pol II ('sitting duck torpedo' mechanism). Disruption of PP1 binding (PNUTS W401A) causes genome-wide transcription acceleration and Spt5 hyper-phosphorylation. Genome-wide elongation rate measurement (TT-seq/metabolic labeling), ChIP-seq, mutant cell lines, PP1-binding mutation Molecular cell High 31677974
2019 MYC directly binds SPT5 and recruits SPT5 to promoters, enabling CDK7-dependent transfer of SPT5 onto Pol II to promote fast and processive transcription elongation. At oncogenic MYC levels, SPT5 is sequestered into non-functional complexes decreasing expression of growth-suppressive genes. Mass spectrometry of MYC and Pol II complexes, co-immunoprecipitation, ChIP-seq, elongation rate measurements Molecular cell High 30928206
2021 Acute depletion of SPT5 triggers ubiquitination and proteasomal degradation of the core Pol II subunit RPB1 specifically at promoter-proximal regions, mediated by E3 ligase Cullin 3, unfoldase VCP/p97, and a CDK9 kinase complex. This demonstrates that SPT5 stabilizes Pol II at promoter-proximal regions and is required for Pol II release into gene bodies. Auxin-inducible degron depletion, ubiquitination assay, proteasome inhibitor rescue, genetic complementation in yeast (evolutionary conservation), ChIP Molecular cell High 34480849
2021 Rapid SPT5 depletion causes pronounced reduction of paused Pol II at both promoters and enhancers, distinct from NELF depletion; impairs transcription activation; alters enhancer chromatin landscape; and causes Pol II processivity defects in gene bodies. Phosphorylation of SPT5 linker Ser666 by P-TEFb promotes pause release; this is antagonized by Integrator-PP2A (INTAC) targeting SPT5 and Pol II. SPT5 C-terminal region phosphorylation links to 3' end termination. Rapid degradation (dTAG system), ChIP-seq, PRO-seq, ATAC-seq, phospho-mutant analysis Molecular cell High 34534457
2010 Spt5 interacts in vivo with the elongating form of RNA Pol II, and mutations in SPT4 or SPT5 reduce cotranscriptional recruitment of the RNA-binding protein She2p to the ASH1 gene, disrupting ASH1 mRNA localization to the bud tip and Ash1p sorting to the daughter nucleus. Co-immunoprecipitation (She2p with elongating Pol II via Spt4-Spt5), ChIP, fluorescence microscopy of mRNA localization Genes & development Medium 20713510
2010 Spt5 directly associates with RNA Pol I and RNA Pol II in yeast through its central region containing NusG N-terminal homology (NGN) and KOW domains. Far Western blotting identifies A190 of Pol I and Rpb1 of Pol II as direct Spt5-binding subunits. Spt5 also directly binds the Pol I initiation factor Rrn3 and ribosomal RNA. Far Western blot, direct binding assay, deletion analysis, genetic suppression assay The Journal of biological chemistry Medium 21467036
2010 AID interacts with Spt5, and Spt5 facilitates the association between AID and stalled RNA Pol II. shRNA screen identifies Spt5 as required for class switch recombination. ChIP-seq shows Spt5 colocalizes with AID and stalled Pol II, and Spt5 accumulation at sites of Pol II stalling predicts AID-induced mutation. shRNA screen, co-immunoprecipitation, ChIP-seq Cell High 20887897
2012 The Spt5 C-terminal repeat region (CTR) is required for normal recruitment of pre-mRNA cleavage factor I (CFI) to 3' ends of S. cerevisiae genes. The CTR interacts with CFI in vitro. CFI occupancy peaks ~100 nt downstream of polyadenylation sites, likely from simultaneous binding to Spt5 CTR, nascent RNA, and Pol II phosphorylated at Ser2. ChIP, genome-wide ChIP profiling, in vitro binding assay Molecular and cellular biology Medium 22290438
2013 A highly conserved domain of yeast Rtf1 directly mediates a physical interaction with the Spt5 CTR. Mutations in this Rtf1 domain or deletion of the Spt5 CTR disrupt the Rtf1-Spt5 interaction and release Paf1C from chromatin. In vitro experiments confirm the direct Rtf1-Spt5 CTR interaction. Co-immunoprecipitation, in vitro direct binding assay, ChIP, mutagenesis Molecular and cellular biology High 23775116
2014 Spt5 interacts with RNAP II through its KOW4-5 domains (contacting Rpb4/7 subcomplex) and through contacts with Rpb1 and Rpb2 at the clamp, protrusion, and wall domains, mapped by site-specific photocrosslinking with the unnatural amino acid p-benzoyl-L-phenylalanine. Deletion of KOW4-5 decreases transcription elongation and derepresses transcription-coupled DNA repair. Site-specific photocrosslinking with unnatural amino acid, genetic deletion analysis, TCR assay Nucleic acids research High 24813444
2014 Crystal structure of fission yeast RNA guanylyltransferase (GTase) bound to Spt5 CTD reveals a distinct docking site on the OB-fold domain that captures the Trp4 residue of the Spt5 nonapeptide repeat. A disruptive GTase mutation in the Spt5 CTD-binding site is synthetically lethal with mutations in the Pol2 CTD-binding site. Thr1 phosphorylation of Spt5 CTD inhibits GTase binding while Ser5-PO4 of Pol2 CTD is required. X-ray crystallography, genetic interaction (synthetic lethality), in vitro binding assays, mutagenesis Genes & development High 24939935
2003 Fission yeast Cdk9/Pch1 (ortholog of metazoan P-TEFb CDK9) phosphorylates the Spt5 CTD specifically on threonine at position 1 (Thr1) within each nonapeptide repeat. CDK9 also phosphorylates the Pol II CTD Ser residues. Autophosphorylation of both Cdk9 and its cyclin partner Pch1 was documented. In vitro kinase assay with CTD peptides and truncation mutants, phosphoamino acid analysis, mutagenesis of kinase active site The Journal of biological chemistry High 12904290
2010 Deletion of the S. pombe Spt5 CTD results in slow growth and aberrant morphology, exacerbated by Pol II CTD truncation and rescued by capping enzyme overexpression, demonstrating overlapping functional roles of the Spt5 and Pol II CTDs in capping enzyme recruitment. The Spt5 CTD T1A mutation abolishes Cdk9 phosphorylation without affecting capping enzyme binding, and has a distinct positive role in elongation. Genetic analysis (deletion, alanine scanning mutagenesis, synthetic interaction), capping enzyme overexpression rescue, 6-AU sensitivity Molecular and cellular biology Medium 20231361
2015 Crystal structures of KOW1-Linker1 (K1L1) and KOW2-KOW3 domains of yeast Spt5 reveal that K1L1 displays a positively charged patch (PCP) that binds nucleic acids in vitro. The PCP is important for in vivo function and partially overlaps functionally with Spt4, suggesting KOW1 and Spt4 form functionally redundant upstream contacts during elongation. X-ray crystallography, in vitro nucleic acid binding assay, genetic growth assay Molecular and cellular biology High 26217010
2017 Spt5 depletion in S. pombe causes RNAPII accumulation in the first ~500 bp of genes, widespread antisense transcription initiating in this barrier region, and reduced elongation rate genome-wide, demonstrating Spt5 is required for transcription past a 5'-proximal barrier and for suppression of antisense transcription. Auxin-inducible degron depletion, ChIP-seq, RNA-seq, NET-seq, MNase-seq Molecular cell High 28366642
2017 Spt5 KOW4-KOW5 region is essential for promoter-proximal pausing, and KOW5 directly contacts the nascent transcript (RNA cross-linking). KOW2-3 domain mediates NELF recruitment to the elongation complex. KOW1 interaction with upstream DNA helix is required for DSIF association with the Pol II elongation complex. Reconstituted in vitro pausing assay with mutant DSIF, Drosophila nuclear extract complementation, RNA cross-linking The Journal of biological chemistry High 28213523
2019 SPT5 directly interacts with MSL1 (of the Drosophila dosage compensation MSL complex) in vitro, and is required downstream of MSL complex chromatin recruitment for dosage compensation, providing mechanistic support for the elongation model of dosage compensation. Forward genetic screen, in vitro pulldown/interaction assay PLoS genetics Medium 23209435
2022 Spt5 contains an acidic N-terminal tail (Spt5N) with a histone-binding motif required for viability in yeast. Spt5N is sandwiched between the downstream nucleosome and upstream DNA emerging from Pol II, and prevents loss of nucleosomal histones within actively transcribed regions, coupling processive transcription to histone capture and re-deposition. Structural analysis (cryo-EM context), genetic essentiality of Spt5N motif, histone occupancy assay by ChIP The EMBO journal High 35102600
2022 ZWC complex (ZC3H4, WDR82, CK2) preferentially localizes at TSS of active genes via interaction of ZC3H4/WDR82 with S5p Pol II CTD, and phosphorylates the N-terminal acidic domain of SPT5. This phosphorylation suppresses divergent antisense transcription at gene promoters. Co-IP, ChIP-seq, knockdown (ZC3H4 depletion), in vitro kinase assay, antisense RNA quantification Nucleic acids research Medium 35325203
2022 Spt5 depletion in mouse B cells leads to loss of super-enhancer–promoter physical interaction and Igh gene expression, correlating strictly with loss of enhancer transcription. CRISPRa rescue of enhancer transcription in Spt5-depleted cells restored Igh gene expression, while histone H3K27 acetylation, chromatin accessibility, and Mediator/cohesin at the enhancer were unaffected. Acute Spt5 depletion, 4C/Hi-C (chromatin interaction), CRISPRa rescue, nascent transcription measurement, ChIP-seq Nature genetics High 32251373
2019 Spt5 depletion in mouse embryonic fibroblasts does not cause global elongation defects or decreased rates, but causes dislodging of a fraction of Pol II complexes during elongation specifically at 15–20 kb from the promoter, coinciding with the transition to maximum elongation speed. Long genes show greater dependency on Spt5 for optimal elongation efficiency than short genes. Spt5 depletion (auxin-inducible degron in MEFs), genome-wide elongation rate measurement, ChIP-seq The EMBO journal High 29514850
2019 Spt5 modulates cotranscriptional spliceosome assembly in S. cerevisiae: Spt5 depletion impairs U5 snRNP accumulation at intron-containing genes, reducing stable cotranscriptional spliceosome assembly. Spt5 co-immunoprecipitates with core spliceosomal proteins and all spliceosomal snRNAs. Auxin-inducible degron depletion, ChIP (U5 snRNP), co-immunoprecipitation with spliceosomal snRNAs, splicing assay RNA Medium 31289129
2025 ARMC5 is identified as a CUL3 adaptor required for VCP/p97-dependent degradation of SPT5-depleted, promoter-proximal Pol II. ARMC5 targets promoter-proximal Pol II in a BTB domain-dependent manner, and interaction between ARMC5 and Pol II requires CDK9, supporting a phospho-dependent degradation model of defective promoter-proximal Pol II. Unbiased proteomic screening (mass spectrometry), genome-wide ChIP-seq, biochemical interaction assay, genetic domain analysis (BTB domain) Science advances High 39854452
2025 Phosphorylations of SPT5 in three regions—the KOW4-5 linker, CTR1, and CTR2—coordinately control pause release, elongation speed, and termination. CTR1 phosphorylation loss slows elongation; simultaneous CTR2 loss partially reverses this but adds effects on splicing and termination. Pausing is unaffected by CTR1 loss but increased by CTR2 loss. CRISPR phospho-mutant knock-in in human HCT116 cells, TT-seq (elongation rate), ChIP-seq, splicing and termination assays Molecular cell High 40250441
2023 KOW4 domain of Spt5 promotes Pol II pausing through contact with nascent RNA, while the KOW2-3 domain mediates NELF recruitment to the elongation complex. KOW1 interaction with upstream DNA helix is required for DSIF association with Pol II. A short helical motif in the NGN domain contacts the non-template DNA strand and facilitates pausing. Purified in vitro pausing assay, Drosophila nuclear extract complementation, RNA cross-linking analysis, in vivo Drosophila viability assay The Journal of biological chemistry High 37517697
2025 Xrn2 (RNA exonuclease, torpedo termination factor) engages with Pol II forming a stable complex, and Spt5 stimulates Xrn2 activity to ensure efficient degradation of nascent RNA leading to Pol II dislodgement. Spt5 is also a key factor attenuating expression of non-coding transcripts, coordinates pre-mRNA splicing, and 3'-end processing. Co-immunoprecipitation (Xrn2-Pol II complex), in vitro Xrn2 activity assay, RNA-seq, splicing assay, termination assay Nature communications High 39746995
2023 SEC (super elongation complex) induces SPT5 phase transition into elongation droplets during early elongation. SPT5's disordered domain is required for pause release and gene activation. Depletion of SEC increases SPT5 pausing clusters. Disease-associated SEC mutations impair phase properties of elongation droplets. Live-cell imaging of condensates, phase separation assay in vitro, SEC depletion, fluorescence microscopy EMBO reports Medium 36629390
2019 SPT5 is required for efficient expression of HSV-1 replication-dependent γ2 late genes; siRNA knockdown of SPT5 (but not NELF-E) specifically inhibits HSV-1 late gene expression. DRB treatment reduces co-immunoprecipitation of viral ICP27 with SPT5, suggesting SPT5-ICP27 interaction is relevant for late gene expression. siRNA knockdown, RT-qPCR, co-immunoprecipitation The Journal of biological chemistry Medium 28743741
1997 Human SUPT5H protein is reversibly phosphorylated during mitosis, as demonstrated by purification from HeLa cells and analysis of mitotic phosphorylation state. Protein purification from HeLa cells, phosphorylation state analysis in mitotic vs. interphase cells FEBS letters Medium 9199507
2016 O-GlcNAcase (OGA) physically associates with SPT5 and TRIM28/KAP1/TIF1β, forming a purified OGA-SPT5-TIF1β complex with elongation properties in vitro. OGA activity is required for elongation in crude nuclear extract but inhibits elongation in a purified system. Co-immunoprecipitation, in vitro transcription elongation assay, ChIP-seq, protein complex purification The Journal of biological chemistry Medium 27601472
2025 LEDGF/p75 is enriched at paused promoters and prevents phosphorylation of the SPT5 PRD/CTR1 by the super elongation complex (SEC). Deletion of the LEDGF IBD domain increases SEC occupancy and SPT5 PRD phosphorylation at promoters, leading to increased pause release. LEDGF and SEC function cooperatively on distinct SPT5 domains to control the pausing-to-elongation transition. ChIP-seq, phosphorylation assay, domain deletion analysis, CUT&RUN Science advances Medium 39823345
2015 Crystal structure of fission yeast RNA triphosphatase Pct1 in complex with Spt5 CTD reveals two CTD docking sites on the Pct1 homodimer engaging TPAWN segments. Threonine phosphorylation of the Spt5 CTD antagonizes Pct1 binding, establishing a binary Spt5 CTD code where Thr1-PO4 is an 'off' switch for capping enzyme recruitment. X-ray crystallography, in vitro binding assay, phosphorylation competition assay RNA High 25414009
2015 Spt5 CTD Thr1 phosphorylation positively regulates histone H3K4 methylation while having minimal effect on H3K36 methylation in fission yeast. Combined Spt5 and Rpb1 CTD mutations have additive effects on H3K36me, suggesting overlapping roles. Pol II Ser2 phosphorylation by Lsk1/Cdk12 positively regulates H3K36me but negatively regulates H3K4me. Phospho-site mutagenesis (alanine substitutions), histone modification western blot and ChIP, genetic epistasis Nucleic acids research Medium 26275777
2022 Spt5 depletion extends Pol II pausing zones beyond the canonical 40–100 bp window to 0.3–3 kb into genes. Phosphomimetic substitutions in CTR1 diminish pausing throughout genes, while mutations preventing phosphorylation of the Spt5 RNA-binding linker (KOW4-5 domain) strengthen pausing, revealing distinct phospho-isoforms that set the balance between pausing and elongation. Spt5 depletion with phospho-mutant rescue, eNET-seq (elongating polymerase mapping), PTEFb inhibition Molecular cell High 36206739

Source papers

Stage 0 corpus · 100 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
2010 Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 300 20887897
2003 Dual roles for Spt5 in pre-mRNA processing and transcription elongation revealed by identification of Spt5-associated proteins. Molecular and cellular biology 243 12556496
2000 High-resolution localization of Drosophila Spt5 and Spt6 at heat shock genes in vivo: roles in promoter proximal pausing and transcription elongation. Genes & development 236 11040217
2003 Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties. Molecular cell 199 12718890
2000 Spt5 and spt6 are associated with active transcription and have characteristics of general elongation factors in D. melanogaster. Genes & development 195 11040216
2000 Domains in the SPT5 protein that modulate its transcriptional regulatory properties. Molecular and cellular biology 188 10757782
2019 Control of RNA Pol II Speed by PNUTS-PP1 and Spt5 Dephosphorylation Facilitates Termination by a "Sitting Duck Torpedo" Mechanism. Molecular cell 176 31677974
2009 Phosphorylation of the transcription elongation factor Spt5 by yeast Bur1 kinase stimulates recruitment of the PAF complex. Molecular and cellular biology 154 19581288
1991 SPT5, an essential gene important for normal transcription in Saccharomyces cerevisiae, encodes an acidic nuclear protein with a carboxy-terminal repeat. Molecular and cellular biology 148 1840633
2002 Interactions between fission yeast mRNA capping enzymes and elongation factor Spt5. The Journal of biological chemistry 131 11893740
2009 Control of transcriptional elongation and cotranscriptional histone modification by the yeast BUR kinase substrate Spt5. Proceedings of the National Academy of Sciences of the United States of America 125 19365074
2012 The Spt4-Spt5 complex: a multi-faceted regulator of transcription elongation. Biochimica et biophysica acta 117 22982195
2009 RNA-directed DNA methylation requires an AGO4-interacting member of the SPT5 elongation factor family. EMBO reports 116 19343051
2002 Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences. Molecular and cellular biology 102 11809800
2019 MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation. Molecular cell 99 30928206
2002 The elongation factors Pandora/Spt6 and Foggy/Spt5 promote transcription in the zebrafish embryo. Development (Cambridge, England) 95 11923199
2013 Structural basis for Spt5-mediated recruitment of the Paf1 complex to chromatin. Proceedings of the National Academy of Sciences of the United States of America 92 24101474
2021 SPT5 stabilization of promoter-proximal RNA polymerase II. Molecular cell 84 34480849
2021 SPT5 stabilizes RNA polymerase II, orchestrates transcription cycles, and maintains the enhancer landscape. Molecular cell 82 34534457
2017 Spt5 Plays Vital Roles in the Control of Sense and Antisense Transcription Elongation. Molecular cell 81 28366642
2001 Genetic interactions of Spt4-Spt5 and TFIIS with the RNA polymerase II CTD and CTD modifying enzymes in Saccharomyces cerevisiae. Genetics 78 11606527
2012 Pol II CTD kinases Bur1 and Kin28 promote Spt5 CTR-independent recruitment of Paf1 complex. The EMBO journal 71 22796944
1998 Role of the human homolog of the yeast transcription factor SPT5 in HIV-1 Tat-activation. Journal of molecular biology 65 9514752
2008 Core structure of the yeast spt4-spt5 complex: a conserved module for regulation of transcription elongation. Structure (London, England : 1993) 62 19000817
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
2012 The spt5 C-terminal region recruits yeast 3' RNA cleavage factor I. Molecular and cellular biology 59 22290438
2003 Characterization of the Schizosaccharomyces pombe Cdk9/Pch1 protein kinase: Spt5 phosphorylation, autophosphorylation, and mutational analysis. The Journal of biological chemistry 59 12904290
2018 Regulation of RNA polymerase II processivity by Spt5 is restricted to a narrow window during elongation. The EMBO journal 57 29514850
2020 Spt5-mediated enhancer transcription directly couples enhancer activation with physical promoter interaction. Nature genetics 55 32251373
2014 Insights into how Spt5 functions in transcription elongation and repressing transcription coupled DNA repair. Nucleic acids research 55 24813444
2010 Separable functions of the fission yeast Spt5 carboxyl-terminal domain (CTD) in capping enzyme binding and transcription elongation overlap with those of the RNA polymerase II CTD. Molecular and cellular biology 54 20231361
2003 In vivo evidence that defects in the transcriptional elongation factors RPB2, TFIIS, and SPT5 enhance upstream poly(A) site utilization. Molecular and cellular biology 53 14560031
2022 The pausing zone and control of RNA polymerase II elongation by Spt5: Implications for the pause-release model. Molecular cell 49 36206739
1999 Tat-SF1 protein associates with RAP30 and human SPT5 proteins. Molecular and cellular biology 49 10454543
2009 The C-terminal repeat domain of Spt5 plays an important role in suppression of Rad26-independent transcription coupled repair. The Journal of biological chemistry 48 20042611
2014 Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo-activated cells. The Journal of experimental medicine 45 25288395
2011 Yeast transcription elongation factor Spt5 associates with RNA polymerase I and RNA polymerase II directly. The Journal of biological chemistry 44 21467036
2011 The transcription elongation factor Spt5 influences transcription by RNA polymerase I positively and negatively. The Journal of biological chemistry 44 21467039
2014 NusG/Spt5: are there common functions of this ubiquitous transcription elongation factor? Current opinion in microbiology 40 24632072
2004 Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5. Retrovirology 40 15620346
2014 How an mRNA capping enzyme reads distinct RNA polymerase II and Spt5 CTD phosphorylation codes. Genes & development 38 24939935
2012 The DSIF subunits Spt4 and Spt5 have distinct roles at various phases of immunoglobulin class switch recombination. PLoS genetics 36 22570620
2008 Identification of Spt5 target genes in zebrafish development reveals its dual activity in vivo. PloS one 35 18978947
2004 Locus-specific requirements for Spt5 in transcriptional activation and repression in Drosophila. Current biology : CB 35 15380072
2017 Identification of Regions in the Spt5 Subunit of DRB Sensitivity-inducing Factor (DSIF) That Are Involved in Promoter-proximal Pausing. The Journal of biological chemistry 33 28213523
2016 O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1β. The Journal of biological chemistry 32 27601472
2022 The pleiotropic roles of SPT5 in transcription. Transcription 29 35876486
2008 Yeast screens identify the RNA polymerase II CTD and SPT5 as relevant targets of BRCA1 interaction. PloS one 29 18197258
2022 ZWC complex-mediated SPT5 phosphorylation suppresses divergent antisense RNA transcription at active gene promoters. Nucleic acids research 26 35325203
2012 Sub1 associates with Spt5 and influences RNA polymerase II transcription elongation rate. Molecular biology of the cell 25 22973055
2009 Repression of RNA polymerase II elongation in vivo is critically dependent on the C-terminus of Spt5. PloS one 25 19742326
2022 Spt5 histone binding activity preserves chromatin during transcription by RNA polymerase II. The EMBO journal 24 35102600
2015 Structures and Functions of the Multiple KOW Domains of Transcription Elongation Factor Spt5. Molecular and cellular biology 24 26217010
2017 A meiosis-specific Spt5 homolog involved in non-coding transcription. Nucleic acids research 22 28053118
1996 Mutations in the SPT4, SPT5, and SPT6 genes alter transcription of a subset of histone genes in Saccharomyces cerevisiae. Genetics 22 8844144
2019 Spt5 modulates cotranscriptional spliceosome assembly in Saccharomyces cerevisiae. RNA (New York, N.Y.) 21 31289129
1997 Human Supt5h protein, a putative modulator of chromatin structure, is reversibly phosphorylated in mitosis. FEBS letters 21 9199507
2019 Targeting Spt5-Pol II by Small-Molecule Inhibitors Uncouples Distinct Activities and Reveals Additional Regulatory Roles. Molecular cell 20 31564557
2015 Functional interaction of Rpb1 and Spt5 C-terminal domains in co-transcriptional histone modification. Nucleic acids research 19 26275777
1996 Isolation, sequencing, and mapping of the human homologue of the yeast transcription factor, SPT5. Genomics 19 8975720
2022 The transient Spt4-Spt5 complex as an upstream regulator of non-coding RNAs during development. Nucleic acids research 15 35188560
2023 The super elongation complex (SEC) mediates phase transition of SPT5 during transcriptional pause release. EMBO reports 14 36629390
2009 Characterization of the Schizosaccharomyces pombe Spt5-Spt4 complex. RNA (New York, N.Y.) 14 19460865
2012 Mutations in the transcription elongation factor SPT5 disrupt a reporter for dosage compensation in Drosophila. PLoS genetics 13 23209435
2023 Assessment of the roles of Spt5-nucleic acid contacts in promoter proximal pausing of RNA polymerase II. The Journal of biological chemistry 12 37517697
2022 A stepwise haematological screening and whole-exome sequencing reveal multiple mutations from SUPT5H causing an elevation of Hb A2 from a cohort of 47336 individuals. International journal of laboratory hematology 12 36054783
2017 CDK9 and SPT5 proteins are specifically required for expression of herpes simplex virus 1 replication-dependent late genes. The Journal of biological chemistry 12 28743741
2016 Analysis of Subcellular RNA Fractions Revealed a Transcription-Independent Effect of Tumor Necrosis Factor Alpha on Splicing, Mediated by Spt5. Molecular and cellular biology 12 26903558
2014 Fission yeast RNA triphosphatase reads an Spt5 CTD code. RNA (New York, N.Y.) 12 25414009
2024 The CDK9-SPT5 Axis in Control of Transcription Elongation by RNAPII. Journal of molecular biology 11 39147127
2020 SUPT5H Post-Transcriptional Silencing Modulates PIN1 Expression, Inhibits Tumorigenicity, and Induces Apoptosis of Human Breast Cancer Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 11 32961044
2019 The transcription factor Spt4-Spt5 complex regulates the expression of ATG8 and ATG41. Autophagy 11 31462158
2025 SPT5 regulates RNA polymerase II stability via Cullin 3-ARMC5 recognition. Science advances 10 39854452
2019 Characterization of Toxoplasma gondii Spt5 like transcription elongation factor. Biochimica et biophysica acta. Gene regulatory mechanisms 10 30707945
2019 Evidence that Moderate Eviction of Spt5 and Promotion of Error-Free Transcriptional Bypass by Rad26 Facilitates Transcription Coupled Nucleotide Excision Repair. Journal of molecular biology 10 30790631
2014 Elongator and SPT4/SPT5 complexes as proxy to study RNA polymerase II transcript elongation control of plant development. Proteomics 10 24733746
2025 Tripartite phosphorylation of SPT5 by CDK9 times pause release and tunes elongation rate of RNA polymerase II. Molecular cell 9 40250441
2015 Structural and biochemical insights into the DNA-binding mode of MjSpt4p:Spt5 complex at the exit tunnel of RNAPII. Journal of structural biology 9 26433031
2011 Erythropoiesis is regulated by the transcription elongation factor Foggy/Spt5 through gata1 gene regulation. Genes to cells : devoted to molecular & cellular mechanisms 9 21205096
2025 DSIF factor Spt5 coordinates transcription, maturation and exoribonucleolysis of RNA polymerase II transcripts. Nature communications 8 39746995
2025 Pcf11/Spt5 condensates stall RNA polymerase II to facilitate termination and piRNA-guided heterochromatin formation. Molecular cell 8 40015272
2024 RBM22 regulates RNA polymerase II 5' pausing, elongation rate, and termination by coordinating 7SK-P-TEFb complex and SPT5. Genome biology 8 38641822
2020 Spt5 Phosphorylation and the Rtf1 Plus3 Domain Promote Rtf1 Function through Distinct Mechanisms. Molecular and cellular biology 8 32366382
2017 Rpb5 modulates the RNA polymerase II transition from initiation to elongation by influencing Spt5 association and backtracking. Biochimica et biophysica acta. Gene regulatory mechanisms 7 29133017
2025 LEDGF/p75 promotes transcriptional pausing through preventing SPT5 phosphorylation. Science advances 5 39823345
2024 SUPT5H mutations associated with elevation of Hb A2 level: Identification of two novel variants and literature review. Gene 5 38373659
2024 Loss-of-Function Variants in SUPT5H as Modifying Factors in Beta-Thalassemia. International journal of molecular sciences 5 39201615
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
2023 β-Thalassemia Trait Caused by SUPT5H Defects: Another Case Report. Hemoglobin 4 37807711
2023 Spt5 C-terminal repeat domain phosphorylation and length negatively regulate heterochromatin through distinct mechanisms. PLoS genetics 4 37939109
2025 Unusual Causes of β Thalassemia Trait: Discovery of another Three Novel SUPT5H Variants. Hemoglobin 3 40159794
2017 Pho dynamically interacts with Spt5 to facilitate transcriptional switches at the hsp70 locus. Epigenetics & chromatin 3 29208012
2024 Spt5 orchestrates cryptic transcript suppression and transcriptional directionality. Communications biology 2 39438667
2023 Emerging Roles of SPT5 in Transcription. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2 37876219
2023 Binding of small molecule inhibitors to RNA polymerase-Spt5 complex impacts RNA and DNA stability. Journal of computer-aided molecular design 2 37987925

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