Transcriptional regulation of the mouse CSF-1 gene

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Abstract
Research in our laboratory is aimed at understanding the cellular and molecular mechanisms that govern colony stimulating factor‐1 (CSF‐1) gene expression. Our hypothesis is that a basal set of trans‐acting factors is bound to the CSF‐1 gene during fibroblast proliferation, resulting in constitutive CSF‐1 gene expression. Modulation of CSF‐1 gene transcription by growth‐arrest (decrease) or stimulation of growth‐arrested fibroblasts (re‐initiate) is mediated by changes in the basal set of factors bound and/or by the addition of stimulus‐specific factors. We have extended our hypothesis to include other cell types (monocytes) to determine if mechanisms used to control CSF‐1 gene expression in fibroblasts are unique or represent common nontissue‐specific regulatory mechanisms. Analysis of CSF‐1‐CAT reporter constructs in transiently transfected fibroblasts and monocytes was used to identify CSF‐1 genomic sequences that affect transcriptional activity. DNase 1 protection, electrophoretic mobility shift, and methylation interference assays were used to identify the putative cis‐acting elements. Results of our study suggest multiple trans‐acting factors may regulate CSF‐1 gene expression; some may be tissue specific, while others, such as AP1, CTF/NF1, Spl, and Sp3, are shared in common. Mol Reprod Dev 46:39–45, 1997.