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Review
. 2023 May 26;24(11):9330.
doi: 10.3390/ijms24119330.

Genetically Engineered Mice Unveil In Vivo Roles of the Mediator Complex

Leonid A Ilchuk  1 , Marina V Kubekina  1 , Yulia D Okulova  1 , Yulia Yu Silaeva  2 , Victor V Tatarskiy  2 , Maxim A Filatov  1 , Alexandra V Bruter  1   3
Affiliations
Review

Genetically Engineered Mice Unveil In Vivo Roles of the Mediator Complex

Leonid A Ilchuk et al. Int J Mol Sci. .

Abstract

The Mediator complex is a multi-subunit protein complex which plays a significant role in the regulation of eukaryotic gene transcription. It provides a platform for the interaction of transcriptional factors and RNA polymerase II, thus coupling external and internal stimuli with transcriptional programs. Molecular mechanisms underlying Mediator functioning are intensively studied, although most often using simple models such as tumor cell lines and yeast. Transgenic mouse models are required to study the role of Mediator components in physiological processes, disease, and development. As constitutive knockouts of most of the Mediator protein coding genes are embryonically lethal, conditional knockouts and corresponding activator strains are needed for these studies. Recently, they have become more easily available with the development of modern genetic engineering techniques. Here, we review existing mouse models for studying the Mediator, and data obtained in corresponding experiments.

Keywords: Mediator; cyclin-dependent kinase; development; immunity; knockout; metabolism; transcription regulation.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Schematic depiction of the mammalian large Mediator complex (compilation based on PDB molecular structures 6W1S, 7NVR, and 7KPX) in 180° projections and its main interactions with TFs, proteins, and genes discussed in the review. Numbers correspond to the Mediator subunit names. Proteins marked red are discussed in the current article, and the fill color saturation correlates with number of papers on those.
Figure 2
Figure 2
Embryonic lethality caused by Mediator subunits’ knockouts and knockdowns. “E” with a number stands for “Embryonic day #” on which the death took place.
Figure 3
Figure 3
Simplified scheme of hematopoiesis and involved Mediator subunit coding genes.
See this image and copyright information in PMC

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References

    1. Tsai K.-L., Sato S., Tomomori-Sato C., Conaway R.C., Conaway J.W., Asturias F.J. A Conserved Mediator–CDK8 Kinase Module Association Regulates Mediator–RNA Polymerase II Interaction. Nat. Struct. Mol. Biol. 2013;20:611–619. doi: 10.1038/nsmb.2549. - DOI - PMC - PubMed
    1. Freitas K.A., Belk J.A., Sotillo E., Quinn P.J., Ramello M.C., Malipatlolla M., Daniel B., Sandor K., Klysz D., Bjelajac J., et al. Enhanced T Cell Effector Activity by Targeting the Mediator Kinase Module. Science. 2022;378:eabn5647. doi: 10.1126/science.abn5647. - DOI - PMC - PubMed
    1. Richter W.F., Nayak S., Iwasa J., Taatjes D.J. The Mediator Complex as a Master Regulator of Transcription by RNA Polymerase II. Nat. Rev. Mol. Cell Biol. 2022;23:732–749. doi: 10.1038/s41580-022-00498-3. - DOI - PMC - PubMed
    1. Gonzalez D., Hamidi N., Del Sol R., Benschop J.J., Nancy T., Li C., Francis L., Tzouros M., Krijgsveld J., Holstege F.C.P., et al. Suppression of Mediator Is Regulated by Cdk8-Dependent Grr1 Turnover of the Med3 Coactivator. Proc. Natl. Acad. Sci. USA. 2014;111:2500–2505. doi: 10.1073/pnas.1307525111. - DOI - PMC - PubMed
    1. Donner A.J., Ebmeier C.C., Taatjes D.J., Espinosa J.M. CDK8 Is a Positive Regulator of Transcriptional Elongation within the Serum Response Network. Nat. Struct. Mol. Biol. 2010;17:194–201. doi: 10.1038/nsmb.1752. - DOI - PMC - PubMed

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