Alternative titles; symbols
HGNC Approved Gene Symbol: MED4
Cytogenetic location: 13q14.2 Genomic coordinates (GRCh38) : 13:48,075,724-48,095,104 (from NCBI)
The Mediator is a multiprotein coactivator that is required by DNA-binding transcription factors for activation of polymerase II (see 180660)-transcribed genes. MED4 appears to be a core Mediator subunit and is found in nearly all Mediator preparations (summary by Sato et al., 2004).
The vitamin D receptor (VDR; 601769)-interacting protein (DRIP) complex binds nuclear receptors in a completely ligand-dependent manner at the C-terminal alpha-helical region, or activation function-2, of the nuclear receptor's ligand-binding domain (LBD). Several DRIP subunits are also components of related cofactors, such as CRSP (e.g., CRSP3; 605042) (summary by Rachez et al., 1999). Naar et al. (1999) stated that the nuclear hormone-receptor cofactor DRIP is probably identical to the ARC complex.
By SDS-PAGE analysis of nuclear extract-depleted B cells bound to VDR LBD in the presence of vitamin D, followed by mass spectrometry, micropeptide sequence analysis, and EST database searching, Rachez et al. (1999) identified cDNAs encoding 13 DRIPs, including DRIP36. They noted that DRIP36 is nearly identical to the p34 subunit of the mouse 'mediator.' Rachez et al. (1999) concluded that transcriptional regulation by nuclear hormone receptors appears to involve the recruitment of coactivator or repressor complexes or subcomplexes composed of shared polypeptides.
Scott (2001) mapped the MED4 gene to chromosome 13 based on sequence similarity between the MED4 sequence (GenBank AF161475) and a genomic contig (GenBank NT_009825).
Naar, A. M., Beaurang, P. A., Zhou, S., Abraham, S., Solomon, W., Tjian, R. Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature 398: 828-832, 1999. [PubMed: 10235267] [Full Text: https://doi.org/10.1038/19789]
Rachez, C., Lemon, B. D., Suldan, Z., Bromleigh, V., Gamble, M., Naar, A. M., Erdjument-Bromage, H., Tempst, P., Freedman, L. P. Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 398: 824-828, 1999. [PubMed: 10235266] [Full Text: https://doi.org/10.1038/19783]
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]
Scott, A. F. Personal Communication. Baltimore, Md. 3/7/2001.