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Phosphorylation of the estrogen receptor α (ERα) N-terminal transcription activation function AF1 at serine 118 (S118) modulates its activity. We show here that human ERα is phosphorylated by the TFIIH cyclin-dependent kinase in a ligand-dependent manner. Furthermore, the efficient phosphorylation of S118 requires a ligand-regulated interaction of TFIIH with AF2, the activation function located in...