MED26

MED26
Identifiers
Aliases	MED26 , CRSP7, CRSP70, mediator complex subunit 26
External IDs	OMIM: 605043; MGI: 1917875; HomoloGene: 68417; GeneCards: MED26; OMA:MED26 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19p13.11 Start 16,574,907 bp [1] End 16,629,062 bp [1]
Gene location (Mouse) Chr. Chromosome 8 (mouse) [2] Band 8|8 B3.3 Start 73,248,405 bp [2] End 73,302,114 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sperm amniotic fluid buccal mucosa cell tibialis anterior muscle nipple skin of arm mucosa of ileum left testis right testis secondary oocyte Top expressed in seminiferous tubule secondary oocyte primary oocyte spermatocyte zygote spermatid granulocyte muscle of thigh medullary collecting duct renal corpuscle More reference expression data BioGPS n/a
Gene ontology Molecular function transcription coactivator activity transcription coregulator activity protein binding Cellular component mediator complex nucleus nucleoplasm core mediator complex Biological process regulation of transcription by RNA polymerase II transcription initiation from RNA polymerase II promoter regulation of transcription, DNA-templated transcription, DNA-templated positive regulation of nucleic acid-templated transcription positive regulation of gene expression Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9441 70625 Ensembl ENSG00000105085 ENSMUSG00000045248 UniProt O95402 Q7TN02 RefSeq (mRNA) NM_004831 NM_027485 RefSeq (protein) NP_004822 NP_081761 Location (UCSC) Chr 19: 16.57 – 16.63 Mb Chr 8: 73.25 – 73.3 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Med26
solution structure of the n-terminal domain i of mouse transcription elongation factor s-ii protein 3
Identifiers
Symbol	Med26 N-terminal domain
Pfam	PF08711
InterPro	IPR017923
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Mediator subunit 26 Middle domain
Identifiers
Symbol	Med26_M
Pfam	PF15694
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Mediator subunit 26 C-terminal domain
Identifiers
Symbol	Med26_C
Pfam	PF15693
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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.

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]

Activity

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:

• 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.
• PIBP, a small hypothetical protein that could be a phosphoinositide binding protein.
• IWS1, which is thought to function in both transcription initiation and elongation. ^[11]
• 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]

Interactions

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]

References

1. GRCh38: Ensembl release 89: ENSG00000105085 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000045248 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Ryu S, Zhou S, Ladurner AG, Tjian R (February 1999). "The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1". Nature. 397 (6718): 446–450. Bibcode:1999Natur.397..446R. doi:10.1038/17141. hdl: 11858/00-001M-0000-0019-A36A-8 . PMID   9989412. S2CID   4405569.
6. "Entrez Gene: CRSP7 cofactor required for Sp1 transcriptional activation, subunit 7, 70kDa".
7. Takahashi H, Parmely TJ, Sato S, Tomomori-Sato C, Banks CA, Kong SE, et al. (July 2011). "Human mediator subunit MED26 functions as a docking site for transcription elongation factors". Cell. 146 (1): 92–104. doi:10.1016/j.cell.2011.06.005. PMC   3145325 . PMID   21729782.
8. Cermakova K, Veverka V, Hodges HC (January 2023). "The TFIIS N-terminal domain (TND): a transcription assembly module at the interface of order and disorder". Biochemical Society Transactions. 51 (1): 125–135. doi:10.1042/BST20220342. PMC   9987994 . PMID   36651856. S2CID   255969299.
9. 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". The Journal of Biological Chemistry. 275 (40): 31266–31268. doi: 10.1074/jbc.M002595200 . PMID   10811649.
10. Ling Y, Smith AJ, Morgan GT (2006). "A sequence motif conserved in diverse nuclear proteins identifies a protein interaction domain utilised for nuclear targeting by human TFIIS". Nucleic Acids Research. 34 (8): 2219–2229. doi:10.1093/nar/gkl239. PMC   1450333 . PMID   16648364.
11. Cermakova K, Demeulemeester J, Lux V, Nedomova M, Goldman SR, Smith EA, et al. (November 2021). "A ubiquitous disordered protein interaction module orchestrates transcription elongation". Science. 374 (6571): 1113–1121. Bibcode:2021Sci...374.1113C. doi:10.1126/science.abe2913. PMC   8943916 . PMID   34822292.
12. Sato S, Tomomori-Sato C, Parmely TJ, Florens L, Zybailov B, Swanson SK, et al. (June 2004). "A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology". Molecular Cell. 14 (5): 685–691. doi: 10.1016/j.molcel.2004.05.006 . PMID   15175163.
13. Ding N, Tomomori-Sato C, Sato S, Conaway RC, Conaway JW, Boyer TG (January 2009). "MED19 and MED26 are synergistic functional targets of the RE1 silencing transcription factor in epigenetic silencing of neuronal gene expression". The Journal of Biological Chemistry. 284 (5): 2648–2656. doi: 10.1074/jbc.M806514200 . PMC   2631966 . PMID   19049968.

This article incorporates text from the public domain Pfam and InterPro: IPR017923

Further reading

• Näär AM, Beaurang PA, Zhou S, Abraham S, Solomon W, Tjian R (April 1999). "Composite co-activator ARC mediates chromatin-directed transcriptional activation". Nature. 398 (6730): 828–832. Bibcode:1999Natur.398..828N. doi:10.1038/19789. PMID   10235267. S2CID   23646963.
• 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". The Journal of Biological Chemistry. 275 (40): 31266–31268. doi: 10.1074/jbc.M002595200 . PMID   10811649.
• Näär AM, Taatjes DJ, Zhai W, Nogales E, Tjian R (June 2002). "Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation". Genes & Development. 16 (11): 1339–1344. doi:10.1101/gad.987602. PMC   186316 . PMID   12050112.
• Sato S, Tomomori-Sato C, Banks CA, Parmely TJ, Sorokina I, Brower CS, et al. (December 2003). "A mammalian homolog of Drosophila melanogaster transcriptional coactivator intersex is a subunit of the mammalian Mediator complex". The Journal of Biological Chemistry. 278 (50): 49671–49674. doi: 10.1074/jbc.C300444200 . PMID   14576168.
• Tomomori-Sato C, Sato S, Parmely TJ, Banks CA, Sorokina I, Florens L, et al. (February 2004). "A mammalian mediator subunit that shares properties with Saccharomyces cerevisiae mediator subunit Cse2". The Journal of Biological Chemistry. 279 (7): 5846–5851. doi: 10.1074/jbc.M312523200 . PMID   14638676.
• Mo X, Kowenz-Leutz E, Xu H, Leutz A (January 2004). "Ras induces mediator complex exchange on C/EBP beta". Molecular Cell. 13 (2): 241–250. doi: 10.1016/S1097-2765(03)00521-5 . PMID   14759369.
• Sato S, Tomomori-Sato C, Parmely TJ, Florens L, Zybailov B, Swanson SK, et al. (June 2004). "A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology". Molecular Cell. 14 (5): 685–691. doi: 10.1016/j.molcel.2004.05.006 . PMID   15175163.
• Zhang X, Krutchinsky A, Fukuda A, Chen W, Yamamura S, Chait BT, Roeder RG (July 2005). "MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription". Molecular Cell. 19 (1): 89–100. doi: 10.1016/j.molcel.2005.05.015 . PMID   15989967.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi: 10.1016/j.cell.2006.09.026 . PMID   17081983. S2CID   7827573.