Cloning and uterus/oviduct-specific expression of a novel estrogen-regulated gene (ERG1)

The steroid hormone estrogen profoundly influences growth and differentiati on programs in the reproductive tract of cycling and pregnant mamals, It is thought that estrogen exerts its cellular effects by regulating the expres sion of specific target genes. We utilized a messenger RNA differential dis play method to identify the genes whose expression is modulated by estrogen in the preimplantation rat uterus, Here we report the cloning of a novel g ene (ERG1) that is tightly regulated by estrogen in two key reproductive ti ssues, the uterus and oviduct. Spatio-temporal analyses reveal that ERG1 mR NA is expressed in a highly stage-specific manner in the uterus and oviduct , and its expression is restricted to the surface epithelium of both of the se tissues, Nucleotide sequence analysis of the full-length ERG1 cDNA indic ates that it has an open reading frame of 1821 nuceotides encoding a putati ve protein of 607 amino acids with a single transmembrane domain and a shor t cytoplasmic tail. The extracellular part of the protein contains several distinct structural motifs. These include a zona pellucida binding domain, which is present in a number of proteins such as the zona pellucida sperm b inding proteins, and uromodulin, In addition, there is a repeat of a motif called CUB domain, which exists in a number of genes involved in developmen t and differentiation such as bone morphogenetic protein 1 (BMP1), Although the precise function of ERG1 eludes us presently, its unique pattern of ex pression in the uterus and oviduct and its regulation by estrogen, a princi pal reproductive hormone, lead us to speculate that this novel gene plays a n important role in events during the reproductive cycle and early pregnanc y.