| MED15 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | MED15 , ARC105, CAG7A, CTG7A, PCQAP, TIG-1, TIG1, TNRC7, mediator complex subunit 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 607372 MGI: 2137379 GeneCards: MED15 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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 MED15 gene. [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]
The p300-CBP coactivator family in humans is composed of two closely related transcriptional co-activating proteins :
Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes. It was discovered in 1990 in the lab of Roger D. Kornberg, recipient of the 2006 Nobel Prize in Chemistry. Mediator complexes interact with transcription factors and RNA polymerase II. The main function of mediator complexes is to transmit signals from the transcription factors to the polymerase.
The GAL4-UAS system is a biochemical method used to study gene expression and function in organisms such as the fruit fly. It is based on the finding by Hitoshi Kakidani and Mark Ptashne, and Nicholas Webster and Pierre Chambon in 1988 that Gal4 binding to UAS sequences activates gene expression. The method was introduced into flies by Andrea Brand and Norbert Perrimon in 1993 and is considered a powerful technique for studying the expression of genes. The system has two parts: the Gal4 gene, encoding the yeast transcription activator protein Gal4, and the UAS, an enhancer to which GAL4 specifically binds to activate gene transcription.
Transcription initiation factor TFIID subunit 6 is a protein that in humans is encoded by the TAF6 gene.
TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 32kDa, also known as TAF9, is a protein that in humans is encoded by the TAF9 gene.
Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene.
Mediator of RNA polymerase II transcription subunit 24 is an enzyme that in humans is encoded by the MED24 gene.
Mediator of RNA polymerase II transcription subunit 23 is an enzyme that in humans is encoded by the MED23 gene.
Mediator of RNA polymerase II transcription subunit 6 is one of the subunits of the Mediator complex. It is an enzyme that in humans is encoded by the MED6 gene.
Mediator of RNA polymerase II transcription subunit 4 also known as mediator complex subunit 4 (MED4), a component of Mediator or vitamin D3 receptor-interacting protein complex 36 kDa component (DRIP36) is a protein that in humans is encoded by the MED4 gene.
Mediator of RNA polymerase II transcription subunit 17 is an enzyme that in humans is encoded by the MED17 gene.
Mediator of RNA polymerase II transcription subunit 7 is an enzyme that in humans is encoded by the MED7 gene.
Mediator of RNA polymerase II transcription subunit 30 is an enzyme that in humans is encoded by the MED30 gene. It represents subunit Med30 of the Mediator complex and is metazoan-specific, having no homologues in yeasts.
Mediator of RNA polymerase II transcription subunit 25 is an enzyme that in humans is encoded by the MED25 gene.
Mediator of RNA polymerase II transcription subunit 26 is an enzyme that in humans is encoded by the MED26 gene. It forms part of the Mediator complex.
An upstream activating sequence or upstream activation sequence (UAS) is a cis-acting regulatory sequence. It is distinct from the promoter and increases the expression of a neighbouring gene. Due to its essential role in activating transcription, the upstream activating sequence is often considered to be analogous to the function of the enhancer in multicellular eukaryotes. Upstream activation sequences are a crucial part of induction, enhancing the expression of the protein of interest through increased transcriptional activity. The upstream activation sequence is found adjacently upstream to a minimal promoter and serves as a binding site for transactivators. If the transcriptional transactivator does not bind to the UAS in the proper orientation then transcription cannot begin. To further understand the function of an upstream activation sequence, it is beneficial to see its role in the cascade of events that lead to transcription activation. The pathway begins when activators bind to their target at the UAS recruiting a mediator. A TATA-binding protein subunit of a transcription factor then binds to the TATA box, recruiting additional transcription factors. The mediator then recruits RNA polymerase II to the pre-initiation complex. Once initiated, RNA polymerase II is released from the complex and transcription begins.
Memory is commonly referred to as the ability to encode, store, retain and subsequently recall information and past experiences in the human brain. This process involves many proteins, one of which is the Histone-binding protein RbAp48, encoded by the RBBP4 gene in humans.
The NuA4 histone acetyltransferase complex is a protein complex that has histone acetylase activity on chromatin, as well as ATPase, DNA helicase and structural DNA binding activities. The complex is thought to be involved in double-strand DNA break repair. Subunits of the human complex include HTATIP/TIP60, TRRAP, RUVBL1, RUVBL2, beta-actin and BAF53/ACTL6A. In yeast, the complex has 13 subunits, including the catalytic subunit Esa1.
The transactivation domain or trans-activating domain (TAD) is a transcription factor scaffold domain which contains binding sites for other proteins such as transcription coregulators. These binding sites are frequently referred to as activation functions (AFs). TADs are named after their amino acid composition. These amino acids are either essential for the activity or simply the most abundant in the TAD. Transactivation by the Gal4 transcription factor is mediated by acidic amino acids, whereas hydrophobic residues in Gcn4 play a similar role. Hence, the TADs in Gal4 and Gcn4 are referred to as acidic or hydrophobic, respectively.
The Gal4 transcription factor is a positive regulator of gene expression of galactose-induced genes. This protein represents a large fungal family of transcription factors, Gal4 family, which includes over 50 members in the yeast Saccharomyces cerevisiae e.g. Oaf1, Pip2, Pdr1, Pdr3, Leu3.
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