A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells

Members of the CCAAT/enhancer binding protein (C/EBP) family have been shown to regulate the terminal differentiation of adipocytes and hepatocytes. In these cell lineages, high levels of C/EBPα are found only in mature, nondividing cells. Using Western blotting and immunohistochemical staining, we have determined the temporal order of expression for C/EBPα, C/EBPβ, and C/EBPδ in differentiating myelomonocytic marrow cells. These studies show a unique temporal pattern of C/EBP isoform expression in the myeloid lineage. In particular, C/EBPα expression is very high in proliferative myelomonocytic cells, and diminishes during phenotypic maturation. While we have detected C/EBPα, C/EBPβ, and C/EBPδ in multiple myeloid leukemia cell lines, and C/EBPα in normal myeloid cells and in de novo human myeloid leukemias, we have not detected these C/EBP isoforms in either erythroid or lymphoid cells. Finally, we show that C/EBPα, C/EBPβ, and C/EBPδ protein and messenger RNA levels correlate in maturing granulocytic cells. The formation of tissue-specific combinations of C/EBP homodimers and heterodimers may allow this family of transcription factors to regulate different sets of genes in adipocytes, hepatocytes, and myelomonocytes.