Alternative titles; symbols
HGNC Approved Gene Symbol: MED8
Cytogenetic location: 1p34.2 Genomic coordinates (GRCh38) : 1:43,383,917-43,389,800 (from NCBI)
MED8 is a component of the mediator complex, which in S. cerevisiae is composed of more than 20 subunits and is required for transcriptional activation. MED8 can also assemble with elongin B (600787), elongin C (600788), and other subunits to form a ubiquitin ligase complex.
MED8 is a Mediator subunit predicted to reside in the head module (summary by Sato et al., 2004).
Using elongin B and elongin C as bait partners in a yeast 2-hybrid screen, Brower et al. (2002) cloned MED8 from a B-cell cDNA library. The deduced 268-amino acid protein contains a potential elongin BC-box motif. MED8 shares significant similarity throughout its N terminus with S. pombe and S. cerevisiae Med8.
Brower et al. (2002) found that MED8 coprecipitated with NUT2 (MED10; 612382), TRAP80 (603810), and other mediator subunits from a HeLa cell line stably expressing NUT2. MED8 also assembled with elongins B and C, CUL2 (603135), and RBX1 (603814) to reconstitute a ubiquitin ligase. Brower et al. (2002) concluded that MED8 can recruit ubiquitin ligase activity directly to the RNA polymerase II transcriptional machinery.
Kagey et al. (2010) reported that Mediator and cohesin (see SMC1A, 300040) physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect 2 DNA segments. The cohesin-loading factor Nipbl (608667) is associated with mediator-cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by Mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell type-specific DNA loops linked to the gene expression program of each cell.
The International Radiation Hybrid Mapping Consortium mapped the MED8 gene to chromosome 1 (stSG4750).
Brower, C. S., Sato, S., Tomomori-Sato, C., Kamura, T., Pause, A., Stearman, R., Klausner, R. D., Malik, S., Lane, W. S., Sorokina, I., Roeder, R. G., Conaway, J. W., Conaway, R. C. Mammalian mediator subunit mMED8 is an elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase. Proc. Nat. Acad. Sci. 99: 10353-10358, 2002. [PubMed: 12149480] [Full Text: https://doi.org/10.1073/pnas.162424199]
Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., Taatjes, D. J., Dekker, J., Young, R. A. Mediator and cohesin connect gene expression and chromatin architecture. Nature 467: 430-435, 2010. Note: Erratum: Nature 472: 247 only, 2011. [PubMed: 20720539] [Full Text: https://doi.org/10.1038/nature09380]
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]