Mediator of RNA polymerase II transcription subunit 15, also known as Gal11, Spt13 in yeast and PCQAP, ARC105, or TIG-1 in humans is a protein encoded by the MED15gene.[5]
MED15 is a general transcriptional cofactor of the mediator complex involved in RNA polymerase II dependent transcription, originally called Gal11 and Spt13 and found in yeast as an essential factor for Gal4 dependent transactivation by T.Fukasawa and F.Winston labs. Transcription factors Gcn4, Pho4, Msn2, Ino2, members of the Gal4 family - Gal4, Oaf1, Pdr1, and viral VP16 have been reported to interact with yeast MED15.[6]
Most of these transcription factors share the same transactivation domain, 9aaTAD, which directly interacts with KIX domain of the MED15.[7]
Furthermore, human MED15 cooperates in mediator complex (previously known as PC2, ARC, or DRIP) with transcription factors like VP16 and SREBP. Human SREBP regulates sterol responsive gene expression, and this regulatory action is conserved in the genetic model organism C. elegans, a roundworm (homologues MDT-15 and SBP-1). Also in C. elegans, MDT-15 is essential for the response to several stresses (fasting, heavy metal, toxin, and oxidative stress); at least in part the fasting response is conferred by interactions of MDT-15 with nuclear receptors, including NHR-49.[5]
The MED15 gene contains stretches of trinucleotide repeats and is located in the chromosome 22 region which is deleted in DiGeorge's syndrome. Two transcript variants encoding different isoforms have been found for this gene.[5]
Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA (Jul 1997). "cDNAs with long CAG trinucleotide repeats from human brain". Human Genetics. 100 (1): 114–22. doi:10.1007/s004390050476. PMID9225980. S2CID25999127.
Abraham S, Solomon WB (Sep 2000). "A novel glutamine-rich putative transcriptional adaptor protein (TIG-1), preferentially expressed in placental and bone-marrow tissues". Gene. 255 (2): 389–400. doi:10.1016/S0378-1119(00)00292-4. PMID11024300.
Berti L, Mittler G, Przemeck GK, Stelzer G, Günzler B, Amati F, Conti E, Dallapiccola B, Hrabé de Angelis M, Novelli G, Meisterernst M (Jun 2001). "Isolation and characterization of a novel gene from the DiGeorge chromosomal region that encodes for a mediator subunit". Genomics. 74 (3): 320–32. doi:10.1006/geno.2001.6566. PMID11414760.
De Luca A, Conti E, Grifone N, Amati F, Spalletta G, Caltagirone C, Bonaviri G, Pasini A, Gennarelli M, Stefano B, Berti L, Mittler G, Meisterernst M, Dallapiccola B, Novelli G (Jan 2003). "Association study between CAG trinucleotide repeats in the PCQAP gene (PC2 glutamine/Q-rich-associated protein) and schizophrenia". American Journal of Medical Genetics Part B. 116B (1): 32–5. doi:10.1002/ajmg.b.10008. PMID12497610. S2CID28657663.
Kwong J, Lo KW, Chow LS, Chan FL, To KF, Huang DP (Jan 2005). "Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma". International Journal of Cancer. 113 (3): 386–92. doi:10.1002/ijc.20593. PMID15455391. S2CID11628354.
Yang F, Vought BW, Satterlee JS, Walker AK, Jim Sun ZY, Watts JL, DeBeaumont R, Saito RM, Hyberts SG, Yang S, Macol C, Iyer L, Tjian R, van den Heuvel S, Hart AC, Wagner G, Näär AM (Aug 2006). "An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis". Nature. 442 (7103): 700–4. Bibcode:2006Natur.442..700Y. doi:10.1038/nature04942. PMID16799563. S2CID4396081.
Ishikawa H, Tachikawa H, Miura Y, Takahashi N (Sep 2006). "TRIM11 binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105) through the ubiquitin-proteasome system". FEBS Letters. 580 (20): 4784–92. doi:10.1016/j.febslet.2006.07.066. PMID16904669. S2CID33550003.