CLONING, CHROMOSOMAL LOCATION, AND CHARACTERIZATION OF MOUSE E2F1

E2F has been implicated in growth control because of its association w ith the retinoblastoma protein and the presence of E2F binding sites i n the promoters of several growth-regulated genes. Proteins that bind to an E2F site have been cloned from human and mouse cells. However, t hese two proteins (human E2F1 and mouse DP-I) are quite different in s equence. We have now cloned a mouse cDNA encoding a protein 86% identi cal to the human E2F1 protein. The mouse E2F1 cDNA encodes a 430-amino -acid protein with a predicted molecular weight of 46,322 and detects mRNAs of 2.7 and 2.2 kb. Using primers complementary to sequences in t he mouse E2F1 3' untranslated region, we mapped the mouse E2F1 gene to chromosome 2, near the Agouti and c-src loci. To understand the role of the different E2F family members in the growth of mouse NIH 3T3 cel ls, we examined the levels of E2F1 and DP-I mRNAs in different stages of the cell cycle. Since the levels of E2F1 but not DP-I mRNA correlat ed with changes in transcription from the dhfr promoter, we examined w hether E2F1 could activate various growth-regulated promoters. We foun d that E2F1 could activate some (dhfr, thymidine kinase, and DNA polym erase alpha) but not all (thymidylate synthase, cad, and c-myc) of the se promoters. On the basis of changes in levels of E2F1 and its abilit y to transactivate growth-regulated promoters, we propose that E2F1 ma y mediate growth factor-initiated signal transduction.