C/EBPepsilon is a myeloid-specific activator of cytokine, chemokine, and macrophage-colony-stimulating factor receptor genes

• Published in: The Journal of biological chemistry Vol. 273; no. 22; p. 13493
• Main Authors: Williams, S C, Du, Y, Schwartz, R C, Weiler, S R, Ortiz, M, Keller, J R, Johnson, P F
• Format: Journal Article
• Language: English
• Published: United States 29.05.1998
• Subjects: Amino Acid Sequence; Animals; Base Sequence; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Chemokine CCL2 - genetics; Chemokine CCL3; Chemokine CCL4; Cloning, Molecular; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Interleukin-6 - genetics; Lipopolysaccharides - pharmacology; Macrophage Inflammatory Proteins - genetics; Mice; Molecular Sequence Data; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Rats; Receptor, Macrophage Colony-Stimulating Factor - genetics; Receptors, Chemokine - genetics; Receptors, Cytokine - genetics; Sequence Homology, Amino Acid
• ISSN: 0021-9258

C/EBPepsilon is a member of the CCAAT/enhancer binding protein family of basic region/leucine zipper transcriptional activators. The C/EBPepsilon protein is highly conserved between rodents and humans, and its domain structure is very similar to C/EBPalpha. In mice C/EBPepsilon mRNA is only detected in hematopoietic tissues, including embryonic liver and adult bone marrow and spleen. Within the hematopoietic system, C/EBPepsilon is expressed primarily in myeloid cells, including promyelocytes, myelomonocytes, and their differentiated progeny. To identify potential functions of C/EBPepsilon, cell lines over-expressing the C/EBPepsilon protein were generated in the P388 lymphoblastic cell line. In contrast to the parental cell line, C/EBPepsilon-expressing cell lines displayed lipopolysaccharide-inducible expression of the interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) genes as well as elevated basal expression of the MIP-1alpha and MIP-1beta chemokine genes. In the EML-C1 hematopoietic stem cell line, C/EBPepsilon mRNA levels increased as the cells progressed along the myeloid lineage, just preceding activation of the gene encoding the receptor for macrophage-colony-stimulating factor (M-CSFR). M-CSFR expression was stimulated in C/EBPepsilon-expressing P388 cell lines, when compared with either the parental P388 cells or P388 cell lines expressing either C/EBPalpha or C/EBPbeta. These results suggest that C/EBPepsilon may be an important regulator of differentiation of a subset of myeloid cell types and may also participate in the regulation of cytokine gene expression in mature cells.