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Gene Review

SPT4  -  transcription elongation factor SPT4

Saccharomyces cerevisiae S288c

Synonyms: Chromatin elongation factor SPT4, Transcription elongation factor SPT4, YGR063C
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Disease relevance of SPT4


High impact information on SPT4

  • The transcription elongation factor Spt4p antagonizes Isw1p and overcomes the Isw1p dependent pausing of RNAPII at the onset of the elongation cycle [2].
  • These results, taken together with the biochemical identification of a human Spt4-Spt5 complex as a transcription elongation factor (Wada et al. 1998), provide strong evidence that these factors are important for transcription elongation in vivo [3].
  • In this work, we report new genetic and biochemical studies of Spt4, Spt5, and Spt6 that reveal a role for these factors in transcription elongation [3].
  • In addition, we show that spt4, spt5, and spt6 mutants themselves have phenotypes suggesting defects in transcription elongation in vivo [3].
  • The drugs 6-azauracil and mycophenolic acid reduce both the elongation rate and processivity, and this processivity defect is aggravated by mutations in Spt4, TFIIS, and CTDK-1 [4].

Biological context of SPT4

  • The SPT4, SPT5, and SPT6 gene products define a class of transcriptional repressors in Saccharomyces cerevisiae that are thought to function through their effects on chromatin assembly or stability [5].
  • Genetic mapping showed that SPT4 is a previously unidentified gene that maps to chromosome VII, between ADE6 and CLY8 [6].
  • The DNA sequence of the SPT4 gene predicts a protein product of 102 amino acids that contains four cysteine residues positioned similarly to those of zinc binding proteins [6].
  • We established that evolutionarily conserved Saccharomyces cerevisiae SPT4, previously identified in genetic screens for defects in chromosome transmission fidelity (ctf), encodes a new structural component of specialized chromatin at kinetochores and heterochromatic loci, with roles in kinetochore function and gene silencing [7].
  • Using a genome-wide mutagenesis approach, we found that deletion of the SPT4 gene suppresses the rad26 defect [8].

Anatomical context of SPT4

  • Both spt4-138 and spt4 delta strains exhibit synergistic chromosome instability in combination with CEN DNA mutations and show in vitro defects in microtubule binding to minichromosomes [9].
  • Our results suggest that the Spt4-Spt5 complex may help coordinate splicing with transcription under conditions that present kinetic challenges to spliceosome assembly or function [10].

Associations of SPT4 with chemical compounds

  • These results suggest that cleavage, but not read-through, stimulation activity is responsible for all three biologic functions of S-II (i.e. suppression of 6-azauracil sensitivity, induction of the IMD2 gene, and suppression of temperature sensitivity of spt4 null mutant) [11].

Physical interactions of SPT4


Regulatory relationships of SPT4

  • The Spt4p subunit of yeast DSIF stimulates association of the Paf1 complex with elongating RNA polymerase II [13].
  • Only spt4 suppresses a non-Ty insertion at HIS4 [14].

Other interactions of SPT4

  • We investigated relationships between three classes of these factors: (1) transcription elongation factors Spt4-Spt5, TFIIS, and Spt16; (2) the C-terminal heptapeptide repeat domain (CTD) of RNA polymerase II; and (3) protein kinases that phosphorylate the CTD and a phosphatase that dephosphorylates it [15].
  • Spt4p associates with telomeres (TEL) and HMRa loci in a Sir3p-dependent manner and is required for transcriptional gene silencing [7].
  • We show that a human homolog of SPT4 (HsSPT4) complements Scspt4-silencing defects and associates with ScCEN DNA in an Ndc10p-dependent manner [7].
  • Spt4 modulates Rad26 requirement in transcription-coupled nucleotide excision repair [8].
  • Importantly, Spt4p is required for Paf1C occupancy at ARG1 (and other genes) and for Paf1C association with Ser5-phosphorylated Pol II in cell extracts, whereas Spt4p-Pol II association is independent of Paf1C [13].

Analytical, diagnostic and therapeutic context of SPT4


  1. Transcription elongation factor Spt4 mediates loss of phosphorylated RNA polymerase II transcription in response to DNA damage. Jansen, L.E., Belo, A.I., Hulsker, R., Brouwer, J. Nucleic Acids Res. (2002) [Pubmed]
  2. Isw1 chromatin remodeling ATPase coordinates transcription elongation and termination by RNA polymerase II. Morillon, A., Karabetsou, N., O'Sullivan, J., Kent, N., Proudfoot, N., Mellor, J. Cell (2003) [Pubmed]
  3. Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. Hartzog, G.A., Wada, T., Handa, H., Winston, F. Genes Dev. (1998) [Pubmed]
  4. Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo. Mason, P.B., Struhl, K. Mol. Cell (2005) [Pubmed]
  5. Mutations in the SPT4, SPT5, and SPT6 genes alter transcription of a subset of histone genes in Saccharomyces cerevisiae. Compagnone-Post, P.A., Osley, M.A. Genetics (1996) [Pubmed]
  6. Molecular and genetic characterization of SPT4, a gene important for transcription initiation in Saccharomyces cerevisiae. Malone, E.A., Fassler, J.S., Winston, F. Mol. Gen. Genet. (1993) [Pubmed]
  7. Functional roles for evolutionarily conserved Spt4p at centromeres and heterochromatin in Saccharomyces cerevisiae. Crotti, L.B., Basrai, M.A. EMBO J. (2004) [Pubmed]
  8. Spt4 modulates Rad26 requirement in transcription-coupled nucleotide excision repair. Jansen, L.E., den Dulk, H., Brouns, R.M., de Ruijter, M., Brandsma, J.A., Brouwer, J. EMBO J. (2000) [Pubmed]
  9. Faithful chromosome transmission requires Spt4p, a putative regulator of chromatin structure in Saccharomyces cerevisiae. Basrai, M.A., Kingsbury, J., Koshland, D., Spencer, F., Hieter, P. Mol. Cell. Biol. (1996) [Pubmed]
  10. Analysis of a splice array experiment elucidates roles of chromatin elongation factor spt4-5 in splicing. Xiao, Y., Yang, Y.H., Burckin, T.A., Shiue, L., Hartzog, G.A., Segal, M.R. PLoS Comput. Biol. (2005) [Pubmed]
  11. Cleavage, but not read-through, stimulation activity is responsible for three biologic functions of transcription elongation factor S-II. Ubukata, T., Shimizu, T., Adachi, N., Sekimizu, K., Nakanishi, T. J. Biol. Chem. (2003) [Pubmed]
  12. Interactions between fission yeast mRNA capping enzymes and elongation factor Spt5. Pei, Y., Shuman, S. J. Biol. Chem. (2002) [Pubmed]
  13. The Spt4p subunit of yeast DSIF stimulates association of the Paf1 complex with elongating RNA polymerase II. Qiu, H., Hu, C., Wong, C.M., Hinnebusch, A.G. Mol. Cell. Biol. (2006) [Pubmed]
  14. Mutations affecting Ty-mediated expression of the HIS4 gene of Saccharomyces cerevisiae. Winston, F., Chaleff, D.T., Valent, B., Fink, G.R. Genetics (1984) [Pubmed]
  15. Genetic interactions of Spt4-Spt5 and TFIIS with the RNA polymerase II CTD and CTD modifying enzymes in Saccharomyces cerevisiae. Lindstrom, D.L., Hartzog, G.A. Genetics (2001) [Pubmed]
  16. Identification and functional analysis of a Kluyveromyces lactis homologue of the SPT4 gene of Saccharomyces cerevisiae. Hikkel, I., Gbelská, Y., Subík, J. Curr. Genet. (1998) [Pubmed]
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