Transcriptional Activation by the Zinc-Finger Homeodomain ProteinδEF1 in Estrogen Signaling Cascades

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Abstract
The transcription factor delta EF1 is a key player in estrogen-signaling cascades in vertebrates. In this pathway, estrogen induces the expression of the gene encoding delta EF1, and then delta EF1 activates transcription of downstream targets. Yet, the molecular mechanisms of transcriptional activation by delta EF1 have remained obscure. Furthermore, most work has concentrated on the capacity of delta EF1 to repress gene expression, rather than its ability to activate transcription. To investigate this activation potential in an endogenous signaling pathway, we characterized ovalbumin (Ov) gene induction by delta EF1. Gel mobility shift assays demonstrate that delta EF1 binds to the 5' flanking region of the Ov gene at two sites, one at -810 to -806 and one at -152 to -148 with respect to the start point of transcription. Correspondingly, these sites are required for induction by estrogen or by delta EF1 in transfection experiments. Furthermore, the activation potential of delta EF1 is not restricted to the chick homolog, as the human ZEB and the mouse delta EF1 homologs also induce Ov gene expression. To characterize the molecular mechanisms whereby delta EF1 activates gene expression, its C-terminal acidic domain was deleted and shown to be necessary for activation of transcription. Furthermore, the acidic domain has intrinsic activation potential, as it can induce the heterologous thymidine kinase promoter. These data establish delta EF1 as an activator of transcription whose action may be DNA-context and cell-type specific, but not species specific.