MED15
Description
The MED15 (mediator complex subunit 15) is a protein-coding gene located on chromosome 22.
MED15, also known as Gal11, Spt13 in yeast, and PCQAP, ARC105, or TIG-1 in humans, is a protein encoded by the MED15 gene. It is a general transcriptional cofactor of the mediator complex involved in RNA polymerase II dependent transcription. Originally identified in yeast, MED15 was found to be an essential factor for Gal4 dependent transactivation. 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. Most of these transcription factors share the same transactivation domain, 9aaTAD, which directly interacts with the KIX domain of MED15. Human MED15 cooperates in the 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. In C. elegans, MDT-15 (the homologue of human MED15) is essential for the response to several stresses, including 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. 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.
MED15 is a component of the Mediator complex, a crucial coactivator involved in the regulated transcription of almost all RNA polymerase II-dependent genes. Mediator acts as a bridge, relaying information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. It is recruited to promoters through direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. MED15 is essential for cholesterol-dependent gene regulation and positively regulates the Nodal signaling pathway.
MED15 is also known as ARC105, CAG7A, CTG7A, PCQAP, TIG-1, TIG1, TNRC7.
