The zinc finger/homeodomain protein δEF1 mediates estrogen-specific induction of the ovalbumin gene

Regulation of the ovalbumin (Ov) gene is strictly controlled by precise developmental, tissue-specific, and hormonal cues. The Ov gene is transcriptionally activated by four classes of steroid hormones: estrogens, androgens, glucocorticoids, and progestins. Although it has served as a model to study multi-hormone gene regulation for the past 30 years, the pathways that relay each hormone signal to the Ov gene are largely unclear. Extensive linker-scanner and point mutation analysis has revealed elements necessary for its induction by estrogen, androgen, progesterone, or glucocorticoid but has failed to identify any elements that are specific to the action of any one steroid hormone. These observations in conjunction with the observation that the Ov gene is indirectly regulated by steroid hormones suggest that these signals may all induce the same transcription factor. However, here we have identified two cis-acting DNA elements in the 5′ flanking region of the Ov gene that are required for induction by estrogen, but not by androgen or progesterone. These elements span -152 to -146 and -810 to -806 with respect to the start point of transcription. This implies that estrogen induces the Ov gene by a separate pathway than do androgens or progestins. Gel mobility shift assays demonstrate that the estrogen-specific sequences bind the estrogen inducible transcription factor δEF1, suggesting that δEF1 plays a distinct role in mediating the estrogen signal to the Ov gene.