One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells

Members of the small Maf family of transcription factors play important rol es in hematopoiesis. Using transgenic assays, we discovered a tissue-specif ic enhancer 3' to the mafK gene. This enhancer directs mafK transcription i n hematopoietic as well as in developing cardiac muscle cells, and was thus designated the hematopoietic and cardiac enhancer of mafK (HCEK). Only two of four GATA consensus motifs identified within HCEK contributed to enhanc er activity, and both of these sites were required for both cardiac and hem atopoietic transcriptional activation. The expression profile of MafK signi ficantly overlapped that of GATA-1 in hematopoietic cells and of GATA-4/-6 in cardiac tissues. Each of these GATA factors bound with high specificity to both of the critical GATA sites in HCEK. Hence, the mafK gene is regulat ed by different GATA proteins in the hematopoietic and cardiac compartments through the same two GATA-binding sites in HCEK. These data provide the fi rst in vivo demonstration that distinct members of a related transcription factor family activate the tissue-specific expression of a single target ge ne using the same cis-regulatory element.