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MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription.

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Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., Roeder R.G.

Human TRAP/Mediator is a key coactivator for many transcription factors that act through direct interactions with distinct subunits, and MED1/TRAP220 is the main subunit target for various nuclear receptors. Remarkably, the current study shows that MED1/TRAP220 only exists in a TRAP/Mediator subpopulation (less then 20% of the total) that is greatly enriched in specific TRAP/Mediator subunits and is tightly associated with a near stoichiometeric level of RNA polymerase II. Importantly, this MED1/TRAP220-containing holoenzyme supports both basal- and activator-dependent transcription in an in vitro system lacking additional RNA polymerase II. Furthermore, chromatin immunoprecipitation experiments demonstrate an activator-selective recruitment of MED1/TRAP220-containing versus MED1/TRAP220-deficient TRAP/Mediator complexes to estrogen receptor (ER) and p53 target genes, respectively. Finally, RNAi studies show that MED1/TRAP220 is required for ER-mediated transcription and estrogen-dependent breast cancer cell growth. These observations have significant implications for our current understanding of the composition, heterogeneity, and functional specificity of TRAP/Mediator complexes.

Mol. Cell 19:89-100(2005) [PubMed] [Europe PMC]