MOLECULAR-CLONING OF ELK-3, A NEW MEMBER OF THE ETS FAMILY EXPRESSED DURING MOUSE EMBRYOGENESIS AND ANALYSIS OF ITS TRANSCRIPTIONAL REPRESSION ACTIVITY

We isolated a cDNA clone, Elk-3, that encodes a novel Ets transcriptio n factor from 16-day mouse embryos, The deduced amino acid sequence of the protein was homologous to human ELK-1 and SAP-1. This protein, EL K-1, and SAP-1 shared some unique structural properties such as an Ets DNA-binding site in the aminoterminal region, a serum response factor interacting domain and phosphorylation sites of serine or threonine r esidues in the carboxy-terminal region. Northern blotting weakly revea led that two transcripts of 4 and 2.1 kb are expressed in the adult ov ary and lung and a 2.1-kb transcript predominated in 8- to 14-day embr yos. We assayed the transcriptional activities of Elk-3 protein on the cytokeratin EndoA enhancer containing Ets binding sites in endodermal cells. Elk-3 protein strongly repressed enhancer activity but did not affect the activity of the basal promoter in the absence of the enhan cer. Furthermore, Elk-3 can suppress the activity of Ets-2 as the tran scriptional activator on the EndoA enhancer. These data suggested that the Elk-3 gene product plays a role in transcriptional regulation dur ing embryogenesis.