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

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. J. Cell. Biochem. 73:49–55, 1999. © 1999 Wiley‐Liss, Inc.

[1]  W. Nacken,et al.  The Gene Encoding the Myeloid-related Protein 14 (MRP14), a Calcium-binding Protein Expressed in Granulocytes and Monocytes, Contains a Potent Enhancer Element in the First Intron* , 1998, The Journal of Biological Chemistry.

[2]  C. Geczy,et al.  Induction of the S100 chemotactic protein, CP-10, in murine microvascular endothelial cells by proinflammatory stimuli. , 1997, Blood.

[3]  C. Sorg,et al.  Electroporation efficiency in mammalian cells is increased by dimethyl sulfoxide (DMSO). , 1996, Nucleic acids research.

[4]  C. Heizmann,et al.  The S100 family of EF-hand calcium-binding proteins: functions and pathology. , 1996, Trends in biochemical sciences.

[5]  T. Kimura,et al.  A novel calcium-binding protein in amniotic fluid, CAAF1: its molecular cloning and tissue distribution. , 1996, Journal of cell science.

[6]  D. Zimmer,et al.  The S100 protein family: History, function, and expression , 1995, Brain Research Bulletin.

[7]  M. Goebeler,et al.  Expression of the calcium-binding proteins MRP8 and MRP14 in monocytes is regulated by a calcium-induced suppressor mechanism. , 1994, The Biochemical journal.

[8]  R. Hromas,et al.  Characterization of the DNA-binding properties of the myeloid zinc finger protein MZF1: two independent DNA-binding domains recognize two DNA consensus sequences with a common G-rich core , 1994, Molecular and cellular biology.

[9]  S. Orkin,et al.  DNA-binding specificity of GATA family transcription factors , 1993, Molecular and cellular biology.

[10]  L. Zon,et al.  Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription , 1993 .

[11]  M. Goebeler,et al.  Expression of calcium-binding proteins MRP8 and MRP14 is associated with distinct monocytic differentiation pathways in HL-60 cells. , 1993, Biochemical and biophysical research communications.

[12]  N. Hogg,et al.  MRP‐8 and MRP‐14, two abundant Ca2+‐binding proteins of neutrophils and monocytes , 1993, Journal of leukocyte biology.

[13]  T. Quertermous,et al.  Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells. , 1991, The Journal of biological chemistry.

[14]  S. Fleming,et al.  Morphological evidence for calcium‐dependent association of calgranulin with the epidermal cytoskeleton in inflammatory dermatoses , 1991, The British journal of dermatology.

[15]  N. Hogg,et al.  Monoclonal antibody 5.5 reacts with p8,14, a myeloid molecule associated with some vascular endothelium , 1989, European journal of immunology.

[16]  C. Hayward,et al.  Expression pattern of two related cystic fibrosis-associated calcium-binding proteins in normal and abnormal tissues. , 1988, Journal of cell science.

[17]  E. Lagasse,et al.  Cloning and expression of two human genes encoding calcium-binding proteins that are regulated during myeloid differentiation , 1988, Molecular and cellular biology.

[18]  R. G. Clerc,et al.  Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis , 1987, Nature.

[19]  P. Brandtzaeg,et al.  Distribution of a formalin-resistant myelomonocytic antigen (L1) in human tissues. II. Normal and aberrant occurrence in various epithelia. , 1987, American journal of clinical pathology.

[20]  Veronica van Heyningen,et al.  A clue to the basic defect in cystic fibrosis from cloning the CF antigen gene , 1987, Nature.

[21]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[22]  P. Brandtzaeg,et al.  Epidermal and dermal distribution of a myelomonocytic antigen (L1) shared by epithelial cells in various inflammatory skin diseases. , 1986, Journal of the American Academy of Dermatology.

[23]  E. Lane,et al.  Characteristics of four new human cell lines derived from squamous cell carcinomas of the head and neck. , 1985, Journal of the National Cancer Institute.

[24]  Etsuko Abe,et al.  1α,25-Dihydroxyvitamin D3 induces differentiation of human myeloid leukemia cells , 1981 .

[25]  S. Collins,et al.  Normal functional characteristics of cultured human promyelocytic leukemia cells (HL-60) after induction of differentiation by dimethylsulfoxide , 1979, The Journal of experimental medicine.

[26]  Holger Karas,et al.  TRANSFAC: a database on transcription factors and their DNA binding sites , 1996, Nucleic Acids Res..