Two functionally different protein isoforms are produced from the chicken estrogen receptor-α gene

Abstract

The existence of two forms of the chicken estrogen receptor-α protein (ER-α) in chicken tissues is demonstrated: the previously reported receptor (cER-α form I), which has a size of 66 kDa, and a new form (cER-α form II), which lacks the N-terminal 41 amino acids present in form I and thus gives rise to a protein of 61 kDa. Whereas the 66-kDa protein is the translation product of several cER-α mRNAs (A1-D), the cER-α protein isoform II is encoded by a new cER-α mRNA (A2), which is transcribed in vivo from a specific promoter that is located in the region of the previously assigned translation start site of the cER-α gene. SI nuclease mapping analysis reveals that cER-α mRNA A2 is liver enriched. The resulting cER-α forms I and II differ in their ability to modulate estrogen target gene expression in a promoter- and cell type-specific manner. Whereas cER-α form I activates or represses in a strictly E2-dependent manner, the truncated form is characterized by a partial transactivating or repressing activity in the absence of its ligand. Comparison of the N-terminal coding regions of different vertebrate ER-α reveal a conservation of the translation start methionine of the protein ER-α form II in other oviparous species but not in mammals. The expression of two classes of ER-α transcripts encoding the two ER-α receptor forms in the liver of Xenopus laevis and rainbow trout is demonstrated. Therefore, the existence of two functionally different protein isoforms produced from the ER-α gene is probably a common and specific feature in oviparous species.