Alternative titles; symbols
HGNC Approved Gene Symbol: MED26
Cytogenetic location: 19p13.11 Genomic coordinates (GRCh38) : 19:16,574,919-16,628,204 (from NCBI)
Mediator complexes are evolutionarily conserved regulatory complexes required for transcriptional activation or repression. Mediator complexes exist in multiple functionally distinct forms that share common core subunits. MED26 is an accessory subunit of a Mediator complex involved in transcriptional activation and elongation (summary by Takahashi et al., 2011).
Transcriptional activation by enhancer-binding factors, such as SP1 (189906), requires interaction with the TFIID complex (see TAF2A; 313650). To identify other potential SP1 cofactors, Ryu et al. (1999) developed an in vitro transcription assay consisting of TFIIA (GTF2A1; 600520), RNA polymerase II (pol II) (see POLR2A; 180660), and the basal transcription factors GTF2B (189963), GTF2E (189962), GTF2F (189968), and GTF2H (189972), supplemented with TFIID or TBP (600075). By sequential chromatography, they identified a Mediator complex, which they called CRSP (cofactor required for SP1 activation), that, along with TFIID, was required for efficient activation by SP1. CRSP behaved as a single complex of approximately 700 kD. Ryu et al. (1999) tentatively identified 9 polypeptides as CRSP subunits. Using microsequence peptide analysis, they cloned a CRSP cDNA encoding a 70-kD protein, CRSP7, which they termed CRSP70.
By immunoprecipitation of human cell lines expressing Mediator subunits with epitope tags, Takahashi et al. (2011) found that MED26 coprecipitated with TFIID and 2 ELL (600284)- and EAF (see 608315)-containing complexes: the multimeric super elongation complex (SEC) and another complex containing KIAA0947 and NARG2 (610835). The C-terminal domain (amino acids 421 to 600) of MED26 was sufficient for its assembly into Mediator and interaction with pol II. The MED26 N-terminal domain (NTD), which forms a 4-helix bundle, contained overlapping docking sites for TFIID, SEC, and the non-SEC ELL/EAF-containing complex. The isolated MED26 NTD functioned as a strong activator of reporter gene expression. Knockdown of MED26 in human cell lines and mouse embryonic stem cells reduced cell proliferation and downregulated expression of MYC (190080), HSP70 (see 140550), and SNAI2 (602150). MED26 knockdown also delayed synthesis of HSP70 mRNA in heat-shocked 293T cells. Chromatin immunoprecipitation analysis showed that depletion of MED26 reduced phosphorylation of the pol II C-terminal domain and reduced recruitment of pol II and the SEC components AFF4 (604417) and CDK9 (603251) to both the promoter regions and bodies of the MYC and HSP70 genes. Takahashi et al. (2011) hypothesized that MED26 may function as a molecular switch that interacts first with the pol II initiation complex through direct interactions with TFIID, then exchanges TFIID for pol II elongation factors to facilitate productive elongation.
Hartz (2012) mapped the MED26 gene to chromosome 19p13.11 based on an alignment of the MED26 sequence (GenBank AF104253) with the genomic sequence (GRCh37).
Hartz, P. A. Personal Communication. Baltimore, Md. 1/26/2012.
Ryu, S., Zhou, S., Ladurner, A. G., Tjian, R. The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1. Nature 397: 446-450, 1999. [PubMed: 9989412] [Full Text: https://doi.org/10.1038/17141]
Takahashi, H., Parmely, T. J., Sato, S., Tomomori-Sato, C., Banks, C. A. S., Kong, S. E., Szutorisz, H., Swanson, S. K., Martin-Brown, S., Washburn, M. P., Florens, L., Seidel, C. W., Lin, C., Smith, E. R., Shilatifard, A., Conaway, R. C., Conaway, J. W. Human Mediator subunit MED26 functions as a docking site for transcription elongation factors. Cell 146: 92-104, 2011. [PubMed: 21729782] [Full Text: https://doi.org/10.1016/j.cell.2011.06.005]