Estrogen regulation of Xenopus laevis .gamma.-fibrinogen gene expression

Abstract

Albumin gene expressin in Xenopus is regulated by estrogen through changes in the stability of its mRNA. The goal of the present study was to determine whether a similar pathway regulates .gamma.-fibrinogen. Degenerate oligonucleotides directed to conserved regions of the carboxyl-terminal half (domain D) of human and lamprey .gamma.-fibrinogen were used to isolate a full-length cDNA clone for Xenopus .gamma.-fibrinogen. Analysis of codon utilization from the DNA sequence of this clone revealed that Xenopus .gamma.-fibrinogen mRNA shows the same bias against CG dinucleotides as present in human, but not lamprey, fibrinogen mRNA. Features of the protein shared with the human homologue include all of the cysteine residues, an N-linked glycosylation site at amino acid 50, and 75% sequence identity in domain D. Much of the same region is conserved in lamprey .gamma.-fibrinogen. There is only a single size mRNA encoding .gamma.-fibrinogen in Xenopus, unlike rats where two mRNAs of different length are generated by alternate splicing. Administration of estrogen to male Xenopus results in the disappearance of .gamma.-fibrinogen mRNA from the cytoplasm, with no effect on steady-state levels in the nucleus. This process can be blocked by prior treatment with anti-estrogen, indicating that, like the regulation of serum albumin mRNA, .gamma.-fibrinogen is regulated posttranscriptionally through an estrogen receptor dependent mechanism. It is postulated that a consensus sequence flanking the AAUAAA polyadenylation signal in .gamma.-fibrinogen and the 68- and 74-kda albumin mRNAs, but not vitellogenin or .beta.-globin mRNA, may play a role in the hormonal regulation of mRNA stability.