Ini, a Small Nuclear Protein that Enhances the Response of the Connexin43 Gene to Estrogen

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Abstract
This article describes the structural and functional characterization of Ini (AF495522), a novel highly conserved zinc-finger protein that had been identified by screening an estrogen-induced rat myometrial expression library. Ini localizes to the nucleus of HeLa cells and binds to the proximal connexin43 (cx43) promoter, as demonstrated by EMSA. In addition, transient transfection experiments performed with estrogen receptor alpha (ERalpha) cDNA show that overexpression of Ini enhances, in a dose-dependent fashion, the up-regulation of the cx43 gene by estrogen. On binding to the cx43 promoter, Ini stimulates the transcriptional activating function (AF)-1, but not the AF-2, of the ERalpha. This makes Ini one of the few known coactivators specific for AF-1. Because estrogen up-regulates Ini mRNA in the myometrium, it is likely that Ini's physiological role in this tissue is to modulate the response of the cx43 gene to estrogen. Transfection studies with an Ini antisense construct seem to indicate that Ini plays an additional role in the cellular response to estrogen affecting both AF-1 and AF-2 activities of the ERalpha. This broader effect may be associated with cell cycle progression that in yeast has been shown to require Ini.