A NOVEL, ERYTHROID CELL-SPECIFIC MURINE TRANSCRIPTION FACTOR THAT BINDS TO THE CACCC ELEMENT AND IS RELATED TO THE KRUPPEL FAMILY OF NUCLEAR PROTEINS

We describe a novel erythroid cell-specific cDNA (EKLF [erythroid Krup pel-like factor]) isolated by enriching for genes expressed in a mouse erythroleukemia cell line but not expressed in a mouse monocyte-macro phage cell line. The complete cDNA sequence is predicted to encode a p rotein of approximately 38,000 Da that contains a proline-rich amino d omain and three TFIIIA-like zinc fingers within the carboxy domain. Ad ditional sequence analyses reveal that the EKLF zinc fingers are most homologous to the Kruppel family of transcription factors and also all ow us to predict potential DNA-binding target sites for the EKLF prote in. On the basis of this prediction, we show that EKLF is able to bind the sequence CCA CAC CCT, an essential element of the beta-globin pro moter. Its tissue distribution establishes that the EKLF transcript is expressed only in bone marrow and spleen, the two hematopoietic organ s of the mouse, and analysis of murine cell lines indicates that EKLF expression is limited to erythroid and mast cell lines. Cotransfection assays establish that EKLF transcriptionally activates a target promo ter that contains its DNA-binding site. The tissue expression pattern of EKLF, in conjunction with its function as a transcriptional activat or, strongly suggests that the EKLF protein may be intimately involved in establishment and/or maintenance of the erythroid cell phenotype.