MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300

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Abstract
CBP/p300 recruitment to enhancer‐bound complexes is a key determinant in promoter activation by many transcription factors. We present a novel mechanism of activating such complexes and show that pre‐assembled Elk‐1–p300 complexes become activated following Elk‐1 phosphorylation by changes in Elk‐1–p300 interactions rather than recruitment. It is known that Elk‐1 binds to promoter in the absence of stimuli. However, it is unclear how activation of Elk‐1 by mitogen‐acivated protein kinase (MAPK)‐mediated phosphorylation leads to targeted gene transactivation. We show that Elk‐1 can interact with p300 in vitro and in vivo in the absence of a stimulus through the Elk‐1 C‐terminus and the p300 N‐terminus. Phosphorylation on Ser383 and Ser389 of Elk‐1 by MAPK enhances this basal binding but, most importantly, Elk‐1 exhibits new interactions with p300. These interaction changes render a strong histone acetyltransferase activity in the Elk‐1‐associated complex that could play a critical role in chromatin remodeling and gene activation. The pre‐assembly mechanism may greatly accelerate transcription activation, which is important in regulation of expression of immediate‐early response genes, in particular those involved in stress responses.