4 OF THE 7 ZINC FINGERS OF THE EVI-1 MYELOID-TRANSFORMING GENE ARE REQUIRED FOR SEQUENCE-SPECIFIC BINDING TO GA(C T)AAGA(T/C)AAGATAA/

Expression of the Evi-1 gene is activated in murine myeloid leukemias by retroviral insertions and in human acute myelogenous leukemia by tr anslocations and inversions involving chromosome band 3q26 where the g ene resides. Aberrant expression of the Evi-1 gene has been shown to i nterfere with myeloid differentiation, which is proposed to be the bas is for its role in leukemias. The Evi-1 gene encodes a 145-kDa DNA-bin ding protein containing two domains of seven and three CYS2-His2 zinc fingers. Previous studies identified a portion of the consensus DNA-bi nding sequence for the first domain of zinc fingers. The experiments p resented here extend these studies and demonstrate that the first doma in recognizes a consensus of 15 nucleotides consisting of GA(C/T)AAGA( T/C)AAGATAA. The first three fingers of the first domain do not detect ably bind DNA but contribute to the binding by conferring a relative s pecificity for GACAA verses GATAA in the first position. The first thr ee fingers also contribute to optimal binding of the 15-nucleotide con sensus sequence.