Mediator of RNA polymerase II transcription subunit 26 is an enzyme that in humans is encoded by the MED26gene.[1][2]
It forms part of the Mediator complex.
The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors.[2]
MED26 is a transcriptionelongation factor that increases the overall transcription rate of RNA polymerase II by reactivating transcription elongation complexes that have arrested transcription. It does this through recruiting ELL/EAF- and P-TEFb- containing complexes to promoters via a direct interaction with the N-terminal domain (NTD). The MED26 NTD also binds TFIID, and TFIID and elongation complexes interact with MED26 through overlapping binding sites.
[3]
MED26 NTD may function as a molecular switch contributing to the transition of Pol II into productive elongation.
MED26 (also known as CRSP70 and ARC70), a subunit of the Mediator complex, which is required for the activity of the enhancer-binding protein Sp1.
Elongin A, a subunit of a transcription elongation factor previously known as SIII. It increases the rate of transcription by suppressing transient pausing of the elongation complex.
PPP1R10, a nuclear regulatory subunit of protein phosphatase 1 that was previously known as p99, FB19 or PNUTS.
IWS1, which is thought to function in both transcription initiation and elongation. The TFIIS N-terminal domain is a compact four-helix bundle. The hydrophobic core residues of helices 2, 3, and 4 are well conserved among TFIIS domains, although helix 1 is less conserved.[5]
Interactions
MED26 has been shown to interact with MED8,[6]Cyclin-dependent kinase 8,[6]POLR2A,[6]MED12[6] and MED28.[6] It also acts synergistically to mediate the interaction between REST (a Kruppel-type zinc finger transcription factor that binds to a 21-bp RE1 silencing element present in over 900 human genes) and Mediator.[7]
References
↑Ryu S, Zhou S, Ladurner AG, Tjian R (Feb 1999). "The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1". Nature. 397 (6718): 446–50. doi:10.1038/17141. PMID9989412.
↑Booth V, Koth CM, Edwards AM, Arrowsmith CH (October 2000). "Structure of a conserved domain common to the transcription factors TFIIS, elongin A, and CRSP70". J. Biol. Chem. 275 (40): 31266–8. doi:10.1074/jbc.M002595200. PMID10811649.
Booth V, Koth CM, Edwards AM, Arrowsmith CH (2000). "Structure of a conserved domain common to the transcription factors TFIIS, elongin A, and CRSP70". J. Biol. Chem. 275 (40): 31266–8. doi:10.1074/jbc.M002595200. PMID10811649.
Sato S, Tomomori-Sato C, Banks CA, et al. (2004). "A mammalian homolog of Drosophila melanogaster transcriptional coactivator intersex is a subunit of the mammalian Mediator complex". J. Biol. Chem. 278 (50): 49671–4. doi:10.1074/jbc.C300444200. PMID14576168.
Tomomori-Sato C, Sato S, Parmely TJ, et al. (2004). "A mammalian mediator subunit that shares properties with Saccharomyces cerevisiae mediator subunit Cse2". J. Biol. Chem. 279 (7): 5846–51. doi:10.1074/jbc.M312523200. PMID14638676.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Sato S, Tomomori-Sato C, Parmely TJ, et al. (2004). "A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology". Mol. Cell. 14 (5): 685–91. doi:10.1016/j.molcel.2004.05.006. PMID15175163.
Zhang X, Krutchinsky A, Fukuda A, et al. (2005). "MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription". Mol. Cell. 19 (1): 89–100. doi:10.1016/j.molcel.2005.05.015. PMID15989967.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID17081983.