Identification of epithelial and myeloid-specific DNA elements regulating MRP14 gene transcription.

Abstract

Macrophage migration inhibition factor-related protein 14 (MRP14) is a Ca2+-binding protein of the S-100 family highly abundant in myelomonocytic and epithelial cells. The expression pattern is restricted to myeloid and epithelial cells and therefore the MRP14 gene is ideally suited to study the regulation of gene expression in these cells. We characterized the human MRP14 promoter by using the chloramphenicol acetyltransferase reporter assay system. The analysis was performed in epithelial (TR146) and myeloid (HL-60) cells, and we were successful in mapping positive and negative regulatory elements. The region -114/-419 contains strong myeloid-specific regulatory elements, whereas the domain -600/-1000 enhances the MRP14 transcription in epithelial cells. The sequence -462/-600 accommodates a regulatory element that enhances the promoter activity in both myeloid and epithelial cells. Regions -114/-419 and -1000/-4500 reduce the expression of MRP14 only in epithelial cells, whereas the domains -419/-462 and -4500/-6500 contain down-regulating elements in both, epithelial and myeloid cells. The presented data demonstrate that transcription of the human MRP14 gene is regulated in a complex manner enabling the precise control of the MRP14 level in epithelial and myeloid cells.