Alternative titles; symbols
HGNC Approved Gene Symbol: SUPT5H
Cytogenetic location: 19q13.2 Genomic coordinates (GRCh38) : 19:39,445,582-39,476,670 (from NCBI)
The yeast suppressor of Ty (SPT) genes were isolated based on their ability to suppress insertion of the Ty transposable element. These genes encode a variety of proteins that are involved in chromosome activity, including histones and transcription factors. The SPT genes are not necessarily homologs of one another. SPT4 (603555), SPT5, and SPT6 (601333) are believed to be parts of a protein complex involved in transcriptional repression by modulating chromatin structure. Chiang et al. (1996) and Stachora et al. (1997) cloned and characterized cDNAs encoding the human homolog of yeast SPT5. Chiang et al. (1996) reported that the gene, symbolized SUPT5H, encodes a 1,087-amino acid polypeptide with 50% similarity to yeast SPT5. The N terminus of SUPT5H is highly acidic, while the C terminus contains 7 mitogen-activated protein (MAP) kinase consensus sequences. Stachora et al. (1997) noted that the SUPT5H sequence contains a putative nuclear localization signal. By Northern blotting, Chiang et al. (1996) showed that SUPT5H was expressed as a 4-kb transcript at varying levels in every adult human tissue tested.
Chiang et al. (1998) isolated a cDNA encoding mouse Supt5h. The deduced mouse and human SUPT5H proteins share 97% sequence identity.
Stachora et al. (1997) showed that levels of SUPT5H protein did not vary during the cell cycle of HeLa cells. However, the protein was reversibly phosphorylated during mitosis.
Yamada et al. (2006) showed that D-ribofuranosylbenzimidazole sensitivity-inducing factor (DSIF), a heterodimer of SPT4 and SPT5, repressed or activated transcription elongation by RNA polymerase II in HeLa cells based on the phosphorylation status of SPT5.
Using somatic cell hybrids and radiation hybrids, Chiang et al. (1996) mapped the SUPT5H gene to human chromosome 19q13. Screening of a cosmid contig localized the gene to about 250 kb telomeric to the CLC locus (153310) and about 1 Mb centromeric to the AKT2 oncogene (164731), placing it at 19q13.1. By analysis of an interspecific backcross, Chiang et al. (1996) mapped the Supt5h gene to mouse chromosome 7 in a region showing homology of synteny with human 19q13.1-q13.2.
Guo et al. (2000) described a zebrafish mutant called 'foggy,' which was identified in a genetic screen from mutations that affect neuronal development. The foggy zebrafish displayed a reduction of dopamine-containing neurons and a corresponding surplus of serotonin-containing neurons in the hypothalamus. Positional cloning disclosed that foggy is a brain-enriched nuclear protein that is structurally related to the yeast transcription elongation factor SPT5 and to human SUPT5H. Foggy is a 1,084-amino acids protein, while SUPT5H is 1,087 amino acids. In conserved regions, there is 88 to 96% amino acid identity between zebrafish and human. Foggy is not part of the basic transcription apparatus but is a phosphorylation-dependent dual regulator of transcription elongation. The foggy mutation (val1012 to asp) disrupts its repressive but not its stimulatory activity. Guo et al. (2000) concluded that their results provide molecular, genetic, and biochemical evidence that negative regulators of transcription elongation control key aspects of neuronal development.
Chiang, P.-W., Fogel, E., Jackson, C. L., Lieuallen, K., Lennon, G., Qu, X., Wang, S.-Q., Kurnit, D. M. Isolation, sequencing, and mapping of the human homologue of the yeast transcription factor, SPT5. Genomics 38: 421-424, 1996. [PubMed: 8975720] [Full Text: https://doi.org/10.1006/geno.1996.0646]
Chiang, P.-W., Stubbs, L., Zhang, L., Kurnit, D. M. Isolation of murine SPT5 homologue: completion of the isolation and characterization of human and murine homologues of yeast chromatin structural protein complex SPT4, SPT5, and SPT6. Genomics 47: 426-428, 1998. [PubMed: 9480761] [Full Text: https://doi.org/10.1006/geno.1997.5137]
Guo, S., Yamaguchi, Y., Schilbach, S., Wada, T., Lee, J., Goddard, A., French, D., Handa, H., Rosenthal, A. A regulator of transcriptional elongation controls vertebrate neuronal development. Nature 408: 366-369, 2000. [PubMed: 11099044] [Full Text: https://doi.org/10.1038/35042590]
Stachora, A. A., Schafer, R. E., Pohlmeier, M., Maier, G., Ponstingl, H. Human Supt5h protein, a putative modulator of chromatin structure, is reversibly phosphorylated in mitosis. FEBS Lett. 409: 74-78, 1997. [PubMed: 9199507] [Full Text: https://doi.org/10.1016/s0014-5793(97)00486-9]
Yamada, T., Yamaguchi, Y., Inukai, N., Okamoto, S., Mura, T., Handa, H. P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation. Molec. Cell 21: 227-237, 2006. [PubMed: 16427012] [Full Text: https://doi.org/10.1016/j.molcel.2005.11.024]