Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms' tumor locus

M. A. Harrington, B. Konicek, A. Song, X. L. Xia, W. J. Fredericks, F. J. Rauscher

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Colony-stimulating factor-1 (CSF-1) is a member of the immediate early gene family, which is expressed in mitogen-stimulated quiescent fibroblasts. The biological effects of CSF-1 are multifaceted and include stimulation of the proliferation and differentiation of myeloid progenitors and activity of circulating monocytes and tissue-specific macrophages. Ablation of circulating levels of biologically active CSF-1 in mice leads to osteope-trosis and sterility, thus implicating a role for CSF-1 in bone remodeling and implantation. Identification of regulatory elements and cognate transcription factors that bind the csf-1 promoter and mediate such diverse expression patterns is of great interest. We identified a sequence element at -273 to -265 (relative to the transcription initiation site) in the murine csf-1 promoter, which contains overlapping consensus sequences for the Wilms' tumor protein (WT1), EGR-1, SP1, and SP3 proteins. WT1 and EGR-1 proteins produced in vitro bound to this sequence, and co-transfection of wt1 with a csf-1-cat reporter plasmid resulted in repression of promoter activity. Interestingly, nuclear extracts prepared from serum-stimulated C3H10T1/2 cells contained predominantly SP1 and SP3 binding activities, which recognized the -273 to -265 site. Thus repression of the csf-1 promoter by WT1 at this site may involve competition between SP1 family transcriptional activators and the WT1 repressor. Colony-stimulating factor-1 may be a physiologically relevant target gene for regulation by the WT1 transcription factor.

Original languageEnglish (US)
Pages (from-to)21271-21275
Number of pages5
JournalJournal of Biological Chemistry
Volume268
Issue number28
StatePublished - Jan 1 1993

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Macrophage Colony-Stimulating Factor
Wilms Tumor
Tumors
Transcription Factors
Genes
Proteins
Immediate-Early Genes
Bone Remodeling
Macrophages
Transcription Initiation Site
Consensus Sequence
Fibroblasts
Ablation
Mitogens
Infertility
Transfection
Monocytes
Bone
Cats
Plasmids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Harrington, M. A., Konicek, B., Song, A., Xia, X. L., Fredericks, W. J., & Rauscher, F. J. (1993). Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms' tumor locus. Journal of Biological Chemistry, 268(28), 21271-21275.

Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms' tumor locus. / Harrington, M. A.; Konicek, B.; Song, A.; Xia, X. L.; Fredericks, W. J.; Rauscher, F. J.

In: Journal of Biological Chemistry, Vol. 268, No. 28, 01.01.1993, p. 21271-21275.

Research output: Contribution to journalArticle

Harrington, MA, Konicek, B, Song, A, Xia, XL, Fredericks, WJ & Rauscher, FJ 1993, 'Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms' tumor locus', Journal of Biological Chemistry, vol. 268, no. 28, pp. 21271-21275.
Harrington, M. A. ; Konicek, B. ; Song, A. ; Xia, X. L. ; Fredericks, W. J. ; Rauscher, F. J. / Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms' tumor locus. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 28. pp. 21271-21275.
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