dissociate from mediator. This appears to be accomplished by phosphorylation of part of the polymerase by a kinase. Importantly, mediator and transcription factors do not dissociate from the DNA at the time polymerase begins transcription. Rather, the complex remains at the promoter to recruit another RNA polymerase to begin another round of transcription. There is some evidence to suggest that mediator in a yeast is involved in regulating RNA polymerase III (Pol III) transcripts of tRNAs In support of that evidence, an independent report showed specific association of mediator with Pol III in Saccharomyces cerevisiae. Those authors also reported specific associations with RNA polymerase I and proteins involved in transcription elongation and RNA processing, supporting other evidence of mediator's involvement in elongation and processing. Chromatin organization Mediator is involved in "looping" of chromatin, which brings distant regions of a chromosome into closer physical proximity. The ncRNA-a mentioned above is involved in such looping. Enhancer RNAs (eRNAs) can function similarly. In addition to the looping of euchromatin, mediator appears to be involved in formation or maintenance of heterochromatin at centromeres and telomeres. Signal transduction TGFβ signaling at the cell membrane results in 2 different intracellular pathways. One of them depends on MED15, while the other is independent of MED15. In both human cells and Caenorhabditis elegans MED15 is involved in lipid homeostasis through the pathway involving SREBPs In the model plant Arabidopsis thaliana the ortholog of MED15 is required for signaling by the plant hormone Salicylic acid, while MED25 is required for the transcriptional activation of jasmonate and shade signalling responses. Two components of the CDK module (MED12 and MED13) are involved in the Wnt signaling pathway MED23 is involved in RAS/MAPK/ERK pathway This abbreviated review shows the versatility of individual mediator subunits, and leads to the idea that mediator is an end-point of signaling pathways. Human disease Involvement of mediator in various human diseases has been reviewed. Since inhibiting one interaction of a disease-causing signaling pathway with a subunit of mediator may not inhibit general transcription needed for normal function, mediator subunits are attractive candidates for therapeutic drugs. Interactions A method employing very gentle cell lysis in yeast followed by co-immunoprecipitation with an antibody to a mediator subunit (Med 17) has confirmed almost all previously reported or predicted interactions and revealed many previously unsuspected specific interactions of various proteins with mediator. MED 1 A discussion of all mediator subunits is