Mediator of RNA polymerase II transcription subunit 26 is an enzyme that in humans is encoded by the MED26gene.[5][6] 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.[6]
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.[7] 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.
TFIIS, which rescues RNA polymerase II from backtracked pause states.
The N-terminal domain of MED26 is a protein fold known as a TFIIS N-terminal domain (or TND).[8] It is a compact five-helix bundle. The hydrophobic core residues of helices 2, 3, and 4 are well conserved among TFIIS domains, although helix 1 is less conserved.[10]
MED26 has been shown to interact with MED8,[12]Cyclin-dependent kinase 8,[12]POLR2A,[12]MED12[12] and MED28.[12] 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.[13]
