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Complexity in Transcription Control at the Activation Domain–Mediator Interface

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Science Signaling  05 May 2009:
Vol. 2, Issue 69, pp. ra20
DOI: 10.1126/scisignal.1164302

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Different Partners Elicit Different Responses

The mediator of transcription complex links various DNA-bound transcription factors to RNA polymerase II and associated proteins, enabling signals that modify these transcription factors to regulate gene transcription. For instance, in embryonic stem cells, growth factors in serum activate the mitogen-activated protein kinase (MAPK) signaling pathway, leading to phosphorylation of the ternary complex factor (TCF) ELK1, which interacts with mediator to stimulate transcription of the Egr1 gene. Balamotis et al. observed that, whereas loss of a particular mediator subunit—MED23—nearly abolished serum-stimulated transcription of Egr1 in embryonic stem cells, it failed to do so in mouse embryonic fibroblasts. Further investigation revealed that the relative abundance of ELK1 and two closely related TCFs differed in these two cell types, as did the magnitude and kinetics of Egr1 activation. Activation by the three TCFs showed differential sensitivity to the loss of MED23 and differences in their interactions with mediator revealed by fluorescence microscopy in living cells. Thus, the authors propose that different cell types can modify their transcriptional responses to MAPK signaling by regulating the relative concentrations of these three closely related TCFs.

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