MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription.
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.
Zhang
Xiaoting
X
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Krutchinsky
Andrew
A
Fukuda
Aya
A
Chen
Wei
W
Yamamura
Soichiro
S
Chait
Brian T
BT
Roeder
Robert G
RG
D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D056913:Mediator Complex Subunit 1; D034622:RNA Interference; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C538855:MED1 protein, human; D056913:Mediator Complex Subunit 1; D011960:Receptors, Estrogen; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D008156:Luciferases; D012319:RNA Polymerase II; D004706:Endodeoxyribonucleases; C118712:MBD4 protein, human