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. 2020 Mar 10;21(5):1894. doi: 10.3390/ijms21051894

Figure 1.

Figure 1

Role of the Mediator tail in response to 4-methylcyclohexane methanol (MCHM). (A) Schematic of the Mediator complex. Med15 as part of the tail subcomplex directly interacts with transcription factors (TFs). The middle of the Mediator complex tethers the CDK (cyclin-dependent kinase). The head directly interacts with RNA polymerase II (Pol II) at promoter regions to initiate transcription at transcriptional start sites (TSSs) of genes (gray box). (B) Representation of protein components of the Mediator tail based on structures and modeling [3]. Med2 (red), Med14-CTD (light green), Med3 (purple), Med15 (orange), Med16 (blue), and Med5 (green) comprise the tail of the Mediator complex. From the back view, Med5, Med16, Med15, Med3, and Med2 (in order from farthest to closest to the rest of the Mediator complex) are associated with Med14 (not pictured here). (C) Growth assays of yeast with different components of the Mediator knocked out in BY4741 grown with and without 400 ppm MCHM in rich media (YPD). (D) Growth assays of yeast with different components of the Mediator tail knocked out in BY4741 grown with and without 500 ppm MCHM or 650 ppm in YPD or minimal media supplemented with lysine (YM) + histidine, uracil, leucine and methionine (HULM), respectively. (E) Schematic of the Med15 protein. Above the blue line are polymorphic domains including the KIX domain, polyglutamine domain I (polyQI), polyglutamine/alanine domain (polyQA), polyglutamine domain II (polyQII), and the Mediator activation/association domain (MAD). Under the blue line are the fuzzy domains represented as ABD1-3 (activator-binding domains) in gray outlined boxes [10,11]. The Med15 polymorphic amino acids are drawn below from five genetically diverse yeast. Amino acid numbers are based on S288c. (F) Growth assays of genetically diverse yeast strains in the presence of MCHM on different growth media with increasing concentrations of MCHM. Yeast were spotted in ten-fold dilutions onto YM or YPD. RM11, S288c (GSY147), and AWRI1631 are MATa prototrophs while YJM789 is a MATalpha lys2 strain.