The Mediator of transcriptional regulation was first characterized in yeast and is the central coactivator that enables a response of RNA polymerase II (Pol II) to activators and repressors (Kelleher et al., 1990, Mathur et al., 2011, Richter et al., 2020). As a multi-protein complex, Mediator connects DNA-binding TFs with RNA polymerase II (Pol II) and thus serves as a central hub to regulate diverse aspects of transcription. The overall structure of the Mediator complex involves three major modules (Head, Middle, and Tail). The head and middle modules interact with Pol II, while the tail module interacts with various transcription factors (Khan et al., 2022, Malik et al., 2020). The mediator complex also associates transiently with a CDK8 kinase module (Hasan et al., 2020). The CDK8 module is conserved in all eukaryotes and consists of 4 proteins: CDK8, CYCLIN C (CYCC), MED12, and MED13. The middle module includes MED1, MED4, MED7, MED9, MED10, MED19, MED21, MED26 and MED31 (Richter et al., 2020)
MED26 (also known as CRSP70 and ARC70), 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 its N-terminal domain (NTD) (PFAM domain PF08711.14)(Lens et al. 2017). The MED26 NTD also binds TFIID, and TFIID and elongation complexes interact with MED26 through overlapping binding sites (Takahashi et al., 2011, Lens et al. 2017, Cermakova et al., 2023). In humans, it has been shown that MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. It was found that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. The LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3' end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively (Takahashi et al., 2020)..
A database of Mediator genes/proteins from many animal, fungal, and plant species can be freely accessed at www.nipgr.ac.in/MedProDB (Bhardwaj et al., 2021)
Last updated June 2023 by John Gray
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