ROLE FOR THE RANA-CATESBEIANA HOMOLOG OF C EBP-ALPHA IN THE REPROGRAMMING OF GENE-EXPRESSION IN THE LIVER OF METAMORPHOSING TADPOLES/

During the spontaneous or thyroid hormone (TH)-induced metamorphosis o f Rana catesbeiana, developmental changes occur in its liver that are necessary for the transition of this organism from an ammonotelic larv a to a ureotelic adult. These changes include the coordinated expressi on of genes encoding the urea cycle enzymes carbamyl phosphate synthet ase ICPS-II and ornithine transcarbamylase (OTC). Although the express ion of these genes is dependent on TH, the mechanism(s) by which TH in itiates this tissue-specific response is thought io be indirect and to involve early TH-induced upregulation of a gene(s) encoding a tissue- specific transcription factor(s), which, in turn, upregulates the coor dinated expression of these urea-cycle enzyme genes. Herein, we demons trate that mRNAs encoding the Rana homologue of the mammalian transcri ption factor C/EBP alpha (designated RcC/EBP-1) accumulate early in re sponse io TH and that the product of these mRNAs can bind to and trans activate the promoters of both the Rana CPS-I and OTC genes. These res ults support the contention that the reprogramming of gene expression in the liver of metamorphosing tadpoles involves a TH-induced cascade of gene activity in which RcC/EBP-1 and, perhaps, other transcription factors coordinate the expression of genes, such as those encoding CPS -I and OTC, whose products are characteristic of the adult liver pheno type. (C) 1997 Wiley-Liss, Inc.