Alternative titles; symbols
HGNC Approved Gene Symbol: MED21
Cytogenetic location: 12p11.23 Genomic coordinates (GRCh38) : 12:27,022,558-27,038,951 (from NCBI)
The Mediator is a multiprotein coactivator that is required by DNA-binding transcription factors for transcriptional activation of polymerase II (see 180660)-transcribed genes. MED21 is a Mediator subunit predicted to reside in the middle module and appears to be a core subunit found in nearly all Mediator preparations (summary by Sato et al., 2004).
Transcription of class II genes in S. cerevisiae cells is initiated by a large multisubunit complex containing RNA polymerase II (RNAPII), general transcription factors, and SRB (suppressor of RNA polymerase B) proteins. By searching an EST database for sequences similar to yeast Srb7, Chao et al. (1996) identified partial human SRB7 cDNAs. They used PCR with primers based on the sequences of the partial cDNAs to isolate a lymphocyte cDNA corresponding to the entire SRB7 coding region. The predicted 144-amino acid human protein is 35% identical to yeast Srb7. Although the full-length human cDNA failed to complement a yeast Srb7 deletion, several chimeric cDNAs encoding the N terminus of the human protein and the C terminus of the yeast protein were able to do so. Chao et al. (1996) demonstrated that bovine SRB7 associates with a transcriptionally active 2,000-kD complex containing RNAPII and general transcription factors. Similarly, Maldonado et al. (1996) found that SRB7 is part of a human RNAPII complex containing both transcriptional coactivators and components with roles in DNA repair.
Sun et al. (1998) determined that SRB7, MED6 (602984), RGR1 (300182), and the human homologs of yeast Srb10 and Srb11 (see CDK8, 603184), are part of a complex called NAT (negative regulator of activated transcription) that represses activation of transcription by RNAPII. These authors proposed that the NAT complex is a subcomplex of the RNAPII holoenzyme and its function and regulation is through the RNAPII holoenzyme. They suggested that the RNAPII holoenzyme is a transcriptional control panel capable of responding to specific stimuli. The holoenzyme appears to be capable of integrating and responding to specific signals leading to activation or repression of gene expression.
Chao, D. M., Gadbois, E. L., Murray, P. J., Anderson, S. F., Sonu, M. S., Parvin, J. D., Young, R. A. A mammalian SRB protein associated with an RNA polymerase II holoenzyme. Nature 380: 82-85, 1996. [PubMed: 8598913] [Full Text: https://doi.org/10.1038/380082a0]
Maldonado, E., Shiekhattar, R., Sheldon, M., Cho, H., Drapkin, R., Rickert, P., Lees, E., Anderson, C. W., Linn, S., Reinberg, D. A human RNA polymerase II complex associated with SRB and DNA-repair proteins. Nature 381: 86-89, 1996. Note: Erratum: Nature 384: 384 only, 1996. [PubMed: 8609996] [Full Text: https://doi.org/10.1038/381086a0]
Sato, S., Tomomori-Sato, C., Parmely, T. J., Florens, L., Zybailov, B., Swanson, S. K., Banks, C. A. S., Jin, J., Cai, Y., Washburn, M. P., Conaway, J. W., Conaway, R. C. A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Molec. Cell 14: 685-691, 2004. [PubMed: 15175163] [Full Text: https://doi.org/10.1016/j.molcel.2004.05.006]
Sun, X., Zhang, Y., Cho, H., Rickert, P., Lees, E., Lane, W., Reinberg, D. NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription. Molec. Cell 2: 213-222, 1998. [PubMed: 9734358] [Full Text: https://doi.org/10.1016/s1097-2765(00)80131-8]