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, 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 middle module includes MED1, MED4, MED7, MED9, MED10, MED19, MED21, MED26 and MED31 (Koschubs et al., 2010, Richter 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.

Stem cell specification in plants relies on the precise spatiotemporal control of RNA polymerase II (Pol II)-dependent gene transcription, in which the evolutionarily conserved Mediator coactivator complex plays an essential role. In Arabidopsis thaliana, SHORTROOT (SHR) and SCARECROW (SCR) orchestrate a transcriptional program that determines the fate and asymmetrical divisions of stem cells generating the root ground tissue and also in shoot tissues (Yoon et al., 2022). The Mediator subunit MED31 was found to interact with SCR but not SHR (Zhang et al., 2018). Reduction of MED31 disrupted the spatiotemporal activation of CYCLIND6;1 (CYCD6;1), leading to defective asymmetrical division of stem cells generating ground tissue. MED31 was recruited to the promoter of CYCD6;1 in an SCR-dependent manner and was involved in the formation of a dynamic MED31/SCR/SHR ternary complex through the interface protein SCR. The relative protein abundance of MED31 and SHR in different cell types regulates the dynamic formation of the ternary complex, which provides a tunable switch to strictly control the spatiotemporal transcriptional output. This study helps understand the mechanism by which master transcriptional regulators control organ patterning (Zhang et al., 2018).

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

References:

Khan MSS, Islam F, Chen H, Chang M, Wang D, Liu F, Fu ZQ, Chen J. Transcriptional Coactivators: Driving Force of Plant Immunity. Front Plant Sci. 2022 Jan 28;13:823937. doi: 10.3389/fpls.2022.823937. PMID: 35154230; PMCID: PMC8831314.

Malik N, Ranjan R, Parida SK, Agarwal P, Tyagi AK. Mediator subunit OsMED14_1 plays an important role in rice development. Plant J. 2020 Mar;101(6):1411-1429. doi: 10.1111/tpj.14605. Epub 2019 Dec 12. PMID: 31702850.

Zhang X, Zhou W, Chen Q, Fang M, Zheng S, Scheres B, Li C. Mediator subunit MED31 is required for radial patterning of Arabidopsis roots. Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):E5624-E5633. doi: 10.1073/pnas.1800592115. Epub 2018 May 29. PMID: 29844159; PMCID: PMC6004453.

Yoon EK, Oh J, Lim J. (Don't) Look Up!: Is short-root just a short-root plant? Front Plant Sci. 2022 Nov 17;13:1069996. doi: 10.3389/fpls.2022.1069996. PMID: 36466291; PMCID: PMC9712719.

Hasan ASMM, Vander Schoor JK, Hecht V, Weller JL. The CYCLIN-DEPENDENT KINASE Module of the Mediator Complex Promotes Flowering and Reproductive Development in Pea. Plant Physiol. 2020 Mar;182(3):1375-1386. doi: 10.1104/pp.19.01173. Epub 2020 Jan 21. PMID: 31964799; PMCID: PMC7054868.

Richter WF, Nayak S, Iwasa J, Taatjes DJ. The Mediator complex as a master regulator of transcription by RNA polymerase II. Nat Rev Mol Cell Biol. 2022 Nov;23(11):732-749. doi: 10.1038/s41580-022-00498-3. Epub 2022 Jun 20. PMID: 35725906; PMCID: PMC9207880.

Bhardwaj R, Thakur JK, Kumar S. MedProDB: A database of Mediator proteins. Comput Struct Biotechnol J. 2021 Jul 27;19:4165-4176. doi: 10.1016/j.csbj.2021.07.031. PMID: 34527190; PMCID: PMC8342855.