Alternative titles; symbols
HGNC Approved Gene Symbol: SUPT6H
Cytogenetic location: 17q11.2 Genomic coordinates (GRCh38): 17:28,662,205-28,702,679 (from NCBI)
Chiang et al. (1996) isolated and sequenced SUPT6H and Supt6h, the human and murine homologs of the Saccharomyces cerevisiae and Caenorhabditis elegans genes SPT6 and emb-5, respectively. The human and murine SPT6 homologs are virtually identical, as they share more than 98% identity and more than 99% similarity at the protein level. The derived amino acid sequences of these 2 genes predicted a 1,603-amino acid polypeptide in human and a 1,726-amino acid polypeptide in mouse, respectively. The proteins have a highly acidic 5-prime region, a degenerate SH2 domain, and a leucine zipper, features consistent with a nuclear protein that regulates transcription. Northern blot analysis revealed a 7.0-kb transcript that was expressed constitutively in both mouse and human. Chiang et al. (1996) commented that SUPT6H appears to be functionally analogous to SPT6 and emb-5 and may therefore regulate transcription through establishment or maintenance of chromatin structure.
Andrulis et al. (2002) demonstrated that Drosophila Spt6 copurifies with the exosome, a complex of 3-prime-to-5-prime exoribonucleases that is implicated in the processing of structural RNA and in the degradation of improperly processed pre-mRNA. Immunoprecipitation assays of Drosophila nuclear extracts showed that the exosome also associates with the elongation factor Spt5 (602102) and RNA polymerase II (180660). In vivo, exosome subunits colocalized with Spt6 at transcriptionally active loci on polytene chromosomes during normal development and were strongly recruited to heat-shock loci on gene induction. At higher resolution, chromatin immunoprecipitation analysis showed that the exosome is recruited to transcriptionally active units of heat-shock genes. Andrulis et al. (2002) concluded that their data provided a physical basis for the hypothesis that exosome-mediated pre-mRNA surveillance accompanies transcription elongation.
Kaplan et al. (2003) identified an S. cerevisiae Spt6 mutant that permits aberrant transcription initiation from within coding regions. Transcribed chromatin in the Spt6 mutant was hypersensitive to micrococcal nuclease, and this hypersensitivity was suppressed by mutational inactivation of RNA polymerase II. Kaplan et al. (2003) concluded that their results suggested that Spt6 plays a critical role in maintaining normal chromatin structure during transcription elongation, thereby repressing transcription initiation from cryptic promoters.
By knockdown analysis in HeLa cells, Nakamura et al. (2012) showed that PAAF1 (619772) protected SPT6 from proteasomal degradation and modulated the intracellular level of SPT6 protein during human immunodeficiency virus (HIV)-1 (see 609423) transcription. By protecting SPT6, PAAF1 stabilized it to levels that were sufficient for association with HIV-1 chromatin. PAAF1 physically interacted with the N-terminal region of SPT6 and colocalized with SPT6 to sites of HIV-1 transcription and elongating RNA polymerase II. PAAF1-mediated stabilization of SPT6 was also required for nucleosome reassembly at the HIV-1 promoter and for suppression of aberrant HIV-1 transcription inefficient for protein synthesis. Transcriptional profiling in HeLa cells followed by chromatin immunoprecipitation analysis revealed that PAAF1 and/or SPT6 also regulated cellular genes in a similar fashion to HIV-1 transcription.
By PCR-based analysis of somatic cell hybrids and by fluorescence in situ hybridization, Chiang et al. (1996) mapped the human homolog to 17q11.2.
Segre et al. (1995) detected a cDNA fragment from the Supt6h gene on a mouse YAC that also contained the 'nude' locus. Their data placed Supt6h approximately 100 kb from whn (600838), which is located on mouse chromosome 11. Thus, the Supt6h gene was mapped to mouse chromosome 11B1, which exhibits extensive homology of synteny with proximal human 17q.
Andrulis, E. D., Werner, J., Nazarian, A., Erdjument-Bromage, H., Tempst, P., Lis, J. T. The RNA processing exosome is linked to elongating RNA polymerase II in Drosophila. Nature 420: 837-841, 2002. [PubMed: 12490954] [Full Text: https://doi.org/10.1038/nature01181]
Chiang, P.-W., Wang, S., Smithivas, P., Song, W.-J., Ramamoorthy, S., Hillman, J., Puett, S., Van Keuren, M. L., Crombez, E., Kumar, A., Glover, T. W., Miller, D. E., Tsai, C.-H., Blackburn, C. C., Chen, X.-N., Sun, Z., Cheng, J.-F., Korenberg, J. R., Kurnit, D. M. Identification and analysis of the human and murine putative chromatin structure regulator SUPT6H and Supt6h. Genomics 34: 328-333, 1996. [PubMed: 8786132] [Full Text: https://doi.org/10.1006/geno.1996.0294]
Kaplan, C. D., Laprade, L., Winston, F. Transcription elongation factors repress transcription initiation from cryptic sites. Science 301: 1096-1099, 2003. [PubMed: 12934008] [Full Text: https://doi.org/10.1126/science.1087374]
Nakamura, M., Basavarajaiah, P., Rousset, E., Beraud, C., Latreille, D., Henaoui, I.-S., Lassot, I., Mari, B., Kiernan, R. Spt6 levels are modulated by PAAF1 and proteasome to regulate the HIV-1 LTR. Retrovirology 9: 13, 2012. [PubMed: 22316138] [Full Text: https://doi.org/10.1186/1742-4690-9-13]
Segre, J. A., Nemhauser, J. L., Taylor, B. A., Nadeau, J. H., Lander, E. S. Positional cloning of the nude locus: genetic, physical and transcription maps of the region and mutations in the mouse and rat. Genomics 28: 549-559, 1995. [PubMed: 7490093] [Full Text: https://doi.org/10.1006/geno.1995.1187]