FIG. 9.
Independent construct for tamoxifen-dependent expression of Atoh1. Left: The cmv promoter drives constitutive expression of the ATOH1-ER-DSRED fusion protein, which is sequestered in the cytosol by HSP90 binding to the ER LBD, rendering it inactive. 4-OHT competes with HSP90 and allows the ATOH1-ER-DSRED fusion protein to translocate to the nucleus (right), where it binds to the endogenous 3′ Atoh1 promoter region and expresses endogenous Atoh1 signaling in a feed-forward mechanism. Withdrawal of tamoxifen results in a nucleus-to-cytoplasm translocation of the ATOH1-ER-DSRED fusion protein and inactivation of endogenous Atoh1 signaling. The Atoh1-ER-DsRed construct can be placed under control of different promoters to confer cell-specific expression and/or packaged into viral particles for in vivo infection of a stand-alone inducible Atoh1 expression construct. 4-OHT, 4-hydroxytamoxofen.