A Novel Estrogen Receptor α-Associated Protein, Template-Activating Factor Iβ, Inhibits Acetylation and Transactivation

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Abstract
Estrogen receptor-α (ERα) functions as a ligand-activated transcription factor that alters expression of estrogen-responsive genes in target cells. Numerous regulatory proteins interact with ERα to influence estrogen-mediated transactivation. We have identified a novel coregulatory protein, template-activating factor-Iβ (TAF-Iβ), which binds to ERα in vitro when the receptor is not complexed with an estrogen response element. The central region of TAF-Iβ interacts with both the DNA-binding domain and the carboxy-terminal region of ERα. Coimmunoprecipitation experiments demonstrate that TAF-Iβ is associated with the unoccupied, but not the estrogen-occupied, ERα in MCF-7 breast cancer cells. Overexpression of TAF-Iβ inhibits ERα-mediated transcription in a dose- dependent manner. TAF-Iβ represses p300-mediated acetylation of histones and ERα in vitro and decreases ERα acetylation in vivo. TAF-Iβ also binds to other nuclear receptor superfamily members and represses thyroid hormone receptor β- induced transcription in transient transfection assays. Taken together, these data provide evidence that TAF-Iβ regulates transcription of estrogen- responsive genes by modulating acetylation of histones and ERα and that the effects of TAF-Iβ extend to other nuclear receptor superfamily members as well.

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