ISOLATION, GENOMIC STRUCTURE, AND EXPRESSION OF HUMAN ERYTHROID KRUPPEL-LIKE FACTOR (EKLF)

Erythroid Kruppel-like factor (EKLF) is an essential transcriptional a ctivator that directs high-level expression of the adult beta-globin p romoter by binding to its CACCC element, one of a trio of highly conse rved sequences present in erythroid cell-specific promoters and enhanc ers. This report describes the isolation and characterization of the h uman homolog of murine EKLF. The human EKLF transcription unit shares a number of structural properties with its murine counterpart. Human E KLF is contained within 3 kb of genomic DNA, and its coding region is interrupted by two introns whose locations are conserved with the muri ne gene, The three zinc fingers share >90% sequence similarity with an d are predicted to bind the same target sequence as the mouse EKLF. Th e rest of the protein is proline-rich and retains similar to 70% seque nce similarity to the mouse gene, Human EKLF is expressed in bone marr ow and HEL, JK1, and OCIM1 erythroleukemic cell lines but not in K562 nor in myeloid or lymphoid cell lines, These results indicate that the genomic structure and erythroid-restricted expression of EKLF are hig hly conserved between the murine and human homologues, Availability of human EKLF will enable initiation of studies to molecularly assess wh ether it is functionally compromised in those cases of beta-thalassemi a that contain a normal beta-globin gene locus.