The expression of ets genes has been studied in mouse tissues and regenerating murine liver, an in vivo model for cell proliferation. Our results indicate that (i) the ets-1 and ets-2 loci are transcriptionally active; (ii) the ets-2 locus encodes a major mRNA (3.5 kilobases) and is expressed in most of the tissues examined, whereas the ets-l locus encodes a major 5.3-kilobase and minor 4.0-, 2.5-, and 2.2-kilobase RNA species and is expressed at a high level in thymus; (iii) both ets-1 and ets-2 mRNA are abundant in young proliferating tissues and are greatly reduced in terminally differentiated tissues, except thymus; (iv) compensatory growth of liver induces ets-2 mRNA before DNA synthesis, but after fos and myc induction; and (v) ets-2 mRNA, but not ets-1 mRNA, is stabilized in the presence of cycloheximide during hepatic regeneration. These results suggest that ets-2 gene expression is intrinsically linked with cell proliferation. Thus, ets-2 expression follows a pattern similar to other members of the nuclear oncogene family. During hepatic regeneration, the ets-1 and ets-2 loci are subject to differential regulation.Retroviral oncogenes are derived from normal cellular genes that may be actively involved in cell proliferation and differentiation. Avian erythroblastosis virus, E26, is a replication-defective virus that contains tripartite oncogenes Agag-mybE-ets-Aenv (1, 2). We have previously shown (3,4) that (i) v-ets has two cellular homologues, ets-J and ets-2, localized on two different chromosomes in higher mammals;(ii) the ets-l locus has been mapped to human chromosome 11, mouse chromosome 9, and feline chromosome Dl; the ets-2 locus has been assigned to human chromosome 21, mouse chromosome 16, and feline chromosome C2; (iii) both human ets-J and ets-2 loci are transcriptionally active; and (iv) in acute human leukemia, the ets-J locus has been translocated from chromosome 11 to 4 in t(4;11) (q21;23) region, whereas the ets-2 locus has been translocated from chromosome 21 to chromosome 8 in t(8;21) (q22;23), indicating ets gene products may play a significant role in leukemogenesis (refs. 5-8; for a review, see ref. 8). In contrast to the mammalian genes, the chicken proto-ets locus appears to be contiguous and encodes a major transcript of 7.5 kilobases (kb) (2,3).Using temperature-sensitive mutants of E26 virus, Beug et al. (9) have shown that the v-ets domain of the E26 virus retains the capacity to transform erythroblasts and fibroblasts in vitro. From these results, it has been concluded that products derived from the ets gene loci are involved in erythroid differentiation. However, as indicated, the ets loci in higher mammals are very complex. We do not know how many polypeptides are encoded by the ets gene loci and what function they perform in the cell. To understand the biological function and regulation of the ets genes in higher eukaryotes, we have studied the expression of the ets gene loci in various murine tissues and in liver following partial hepatectomy. Our results indica...
