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/EBP alpha are found only in mature, nondividing cells. Using Western blotting and immunohistochemical staining, we have determined the temporal order of expression for C/EBP alpha, C/EBP beta, and C/EBP delta in differentiating myelomonocytic marrow cells. These studies show a unique temporal pattern of C/EBP isoform expression in the myeloid lineage. In particular, C/EBP alpha expression is very high in proliferative myelomonocytic cells, and diminishes during phenotypic maturation. While we have detected C/EBP alpha, C/EBP beta, and C/EBP delta in multiple myeloid leukemia cell lines, and C/EBP alpha 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/EBP alpha, C/EBP beta, and C/EBP delta 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.
Scott
L M
LM
Division of Pediatric Oncology, Johns Hopkins Oncology Center, Baltimore, MD 21287.
Civin
C I
CI
Rorth
P
P
Friedman
A D
AD
D000954:Antigens, Surface / Q000032:analysis; D015153:Blotting, Western; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D002051:Burkitt Lymphoma / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007938:Leukemia / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007377:Interleukin-3; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors