ECA39 IS REGULATED BY C-MYC IN HUMAN AND BY A JUN FOS HOMOLOG, GCN4, IN YEAST/

myc oncogenes are transcription factors regulating the level of expres sion of other genes, Using a subtraction/coexpression strategy, a muri ne genetic target for Myc regulation was isolated, To further characte rize this target gene, named ECA39, we have recently isolated the huma n, nematode and budding yeast homologs of the mouse gene, The recognit ion site for Myc binding, located 3' to the start site of transcriptio n in the mouse gene, is conserved in the human homolog, Transfection e xperiments demonstrated that the Myc binding site of the human gene, m ediates activation of a reporter gene in response to over-expression o f c-myc, The activation was better executed when the c-Myc binding ele ment was positioned downstream to the promoter, which is the usual pos ition of the c-Myc DNA binding element in its genetic targets, The tis sue specific expression of human ECA39 during embryogenesis is similar to that of the mouse homolog, Moreover, ECA39 is expressed in c-myc i nduced human tumors, It is expressed in Burkitt's lymphoma (where c-my c is translocated and activated) but not in non Burkitt's B-cell lymph oma or in T-cell lymphoma, Thus, it seems that ECA39 is a target for c -myc oncogenesis in humans, In yeast, where c-myc is absent, the ECA39 sequences lack the c-Myc binding element, However, the promoter regio n of the yeast ECA39 harbors several Gcn4 binding elements, Moreover, ECA39 is markedly down regulated in cells deleted for gcn4, and deleti on of Gcn4 binding elements down regulated the transcription from ECA3 9 promoter, We thus suggest that ECA39 is a target for c-Myc regulatio n in mammals, while in yeast the regulator is not c-Myc but the c-Jun/ c-Fos homolog - Gcn4.