Mediator of RNA polymerase II transcription subunit 26 is an enzyme that in humans is encoded by the MED26 gene.[5][6] It forms part of the Mediator complex.
MED26 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | MED26, CRSP7, CRSP70, mediator complex subunit 26 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 605043 MGI: 1917875 HomoloGene: 68417 GeneCards: MED26 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Med26 | |||||||||
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Identifiers | |||||||||
Symbol | Med26 N-terminal domain | ||||||||
Pfam | PF08711 | ||||||||
InterPro | IPR017923 | ||||||||
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Mediator subunit 26 Middle domain | |||||||||
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Identifiers | |||||||||
Symbol | Med26_M | ||||||||
Pfam | PF15694 | ||||||||
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Mediator subunit 26 C-terminal domain | |||||||||
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Identifiers | |||||||||
Symbol | Med26_C | ||||||||
Pfam | PF15693 | ||||||||
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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 transcription elongation 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.
The three structural domains of TFIIS are conserved from yeast to human. The 80 or so N-terminal residues form a protein interaction domain containing a conserved motif, which has been called the LW motif because of the invariant leucine and tryptophan residues it contains. Although the N-terminal domain is not needed for transcriptional activity, a similar sequence has been identified in other transcription factors and proteins that are predominantly nuclear localized.[8][9][10] Specific examples are listed below:
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]