ISOLATION OF A GENE ENCODING A FUNCTIONAL ZINC-FINGER PROTEIN HOMOLOGOUS TO ERYTHROID KRUPPEL-LIKE FACTOR - IDENTIFICATION OF A NEW MULTIGENE FAMILY

We have identified and characterized the gene for a novel zinc finger transcription factor which we have termed lung Kruppel-like factor (LK LF). LKLF was isolated through the use of the zinc finger domain of er ythroid Kruppel-like factor (ELKF) as a hybridization probe and is clo sely related to this erythroid cell-specific gene. LKLF is expressed i n a limited number of tissues, with the predominant expression seen in the lungs and spleen. The gene is developmentally controlled, with ex pression noted in the 7-day embryo followed by a down-regulation at 11 days and subsequent reactivation. A high degree of similarity is note d in the zinc finger regions of LKLF and EKLF. Beyond this domain, the sequences diverge significantly, although the putative transactivatio n domains for both LKLF and EKLF are proline-rich regions. In the DNA- binding domain, the three zinc finger motifs are so closely conserved that the predicted DNA contact sites are identical, suggesting that bo th proteins may bind to the same core sequence. This was further sugge sted by transactivation assays in which mouse fibroblasts were transie ntly transfected with a human beta-globin reporter gene in the absence and presence of an LKLF cDNA construct. Expression of the LKLF gene a ctivates this human beta-globin promoter containing the CACCC sequence previously shown to be a binding site for EKLF. Mutation of this pote ntial binding site results in a significant reduction in the reporter gene expression. LKLF and EKLF can thus be grouped as members of a uni que family of transcription factors which have discrete patterns of ex pression in different tissues and which appear to recognize the same D NA-binding site.