Transcription of the Human Colony-Stimulating Factor-1 Receptor Gene Is Regulated by Separate Tissue-Specific Promoters

• Published in: Blood Vol. 79; no. 3; pp. 586 - 593
• Main Authors: Roberts, W. Mark, Shapiro, Linda H., Ashmun, Richard A., Look, A. Thomas
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.02.1992; The Americain Society of Hematology
• Subjects: Base Sequence; Biological and medical sciences; Blotting, Northern; Cell receptors; Cell structures and functions; Choriocarcinoma - genetics; Cloning, Molecular; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Humans; Molecular and cellular biology; Molecular Sequence Data; Monocytes - physiology; Promoter Regions, Genetic; Receptor, Macrophage Colony-Stimulating Factor - genetics; RNA, Messenger - genetics; RNA, Neoplasm - genetics; Transcription, Genetic; Transfection; Trophoblasts - physiology; Tumor Cells, Cultured; Human; Promoter; Membrane receptor; Regulation(control); Gene; Transcription; Cytokine; Tissue specificity; Macrophage colony stimulating factor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V79.3.586.586

Receptors for macrophage colony-stimulating factor (CSF-1R) are expressed not only by monocytes, macrophages, and their progenitors, but also by placental trophoblasts during fetal development. In monocytes, CSF-1R gene transcripts originate at multiple sites immediately upstream of the gene's coding sequences, whereas in placental cells the transcripts include an additional noncoding exon, located 26 kb upstream near the 3’ end of the B-type platelet-derived growth factor (PDGF) receptor gene. Physically distinct CSF-1R transcription origins suggest separate promoter usage by the two cell types. To identify regulatory elements of these promoters, we fused CSF-1R genomic sequences to bacterial reporter genes and introduced the resulting constructs into human cell lines and mouse fibroblasts. A 775-bp genomic fragment containing CSF-1R placental transcription origins and adjacent upstream sequences mediated reporter gene expression in BeWo choriocarcinoma cells and mouse NIH-3T3 fibroblasts, but not in myeloid or lymphoid cells. By contrast, a 550-bp genomic fragment containing CSF-1R monocyte transcription origins and 5’ flanking sequences directed gene expression in U-937 human myeloid cells, but not in the other cell types. Thus, nucleotide sequences of fewer than 1,000-bp upstream of the two independent CSF-1R transcription origins contain the minimal promoter elements needed to program appropriate tissue-specific expression of reporter genes.© 1992 by The American Society of Hematology.0006-4971/92/7903-0011S3.00/0