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Review
. 2015 Feb 27;43(4):2442-53.
doi: 10.1093/nar/gkv037. Epub 2015 Jan 29.

The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator

Jennifer M Grants  1 , Grace Y S Goh  2 , Stefan Taubert  3
Affiliations
Review

The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator

Jennifer M Grants et al. Nucleic Acids Res. .

Abstract

The Mediator multiprotein complex ('Mediator') is an important transcriptional coregulator that is evolutionarily conserved throughout eukaryotes. Although some Mediator subunits are essential for the transcription of all protein-coding genes, others influence the expression of only subsets of genes and participate selectively in cellular signaling pathways. Here, we review the current knowledge of Mediator subunit function in the nematode Caenorhabditis elegans, a metazoan in which established and emerging genetic technologies facilitate the study of developmental and physiological regulation in vivo. In this nematode, unbiased genetic screens have revealed critical roles for Mediator components in core developmental pathways such as epidermal growth factor (EGF) and Wnt/β-catenin signaling. More recently, important roles for C. elegans Mediator subunits have emerged in the regulation of lipid metabolism and of systemic stress responses, engaging conserved transcription factors such as nuclear hormone receptors (NHRs). We emphasize instances where similar functions for individual Mediator subunits exist in mammals, highlighting parallels between Mediator subunit action in nematode development and in human cancer biology. We also discuss a parallel between the association of the Mediator subunit MED12 with several human disorders and the role of its C. elegans ortholog mdt-12 as a regulatory hub that interacts with numerous signaling pathways.

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Figures

Figure 1.
Figure 1.
Overview of the biological activities of Mediator subunits in C. elegans. The figure summarizes the roles of C. elegans Mediator subunits in developmental and physiological pathways. The model is a hypothetical adaptation of C. elegans Mediator, based on the architecture of human Mediator (14). Subunits labeled with a dashed outline lack apparent C. elegans orthologs. In cases where the homology between yeast and metazoan Mediator subunits is tenuous (13), both C. elegans and yeast names are listed (MDT-24/MED5, MDT-27/MED3 and MDT-29/MED2); note, that the positioning of these three subunits is particularly speculative in our model. Putative functions identified in large-scale genetic screens only (i.e. without further experimental validation) are not listed.
Figure 2.
Figure 2.
mdt-12 is a regulatory hub with links to human disease. C. elegans mdt-12 interacts genetically with multiple signaling pathways, indicating a role as a regulatory hub. In addition, mdt-12 interacts genetically with several additional cellular processes, implying a role as a general buffer against genetic perturbations. Similarly, human MED12 mutations are implicated in multiple developmental diseases or somatic tumors and are associated with perturbed cell signaling. Asterisks (*) indicate genetic interactions with pathways/processes that were identified in a genetic screen (115) but have not been further validated. IEG: immediate-early genes. ID: intellectual disability; IGF: insulin-like growth factor.
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References

    1. Fuda N.J., Ardehali M.B., Lis J.T. Defining mechanisms that regulate RNA polymerase II transcription in vivo. Nature. 2009;461:186–192. - PMC - PubMed
    1. Malovannaya A., Lanz R.B., Jung S.Y., Bulynko Y., Le N.T., Chan D.W., Ding C., Shi Y., Yucer N., Krenciute G., et al. Analysis of the human endogenous coregulator complexome. Cell. 2011;145:787–799. - PMC - PubMed
    1. Spiegelman B.M., Heinrich R. Biological control through regulated transcriptional coactivators. Cell. 2004;119:157–167. - PubMed
    1. O'Malley B.W., Qin J., Lanz R.B. Cracking the coregulator codes. Curr. Opini. Cell Biol. 2008;20:310–315. - PMC - PubMed
    1. Malik S., Roeder R.G. The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation. Nat. Rev. Genet. 2010;11:761–772. - PMC - PubMed

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