TRANSCRIPTIONAL REGULATION OF THE MOUSE CSF-1 GENE

Research in our laboratory is aimed at understanding the cellular and molecular mechanisms that govern colony stimulating factor-1 (CSF-1) g ene expression. Our hypothesis is that a basal set of trans-acting fac tors is bound to the CSF-1 gene during fibroblast proliferation, resul ting in constitutive CSF-1 gene expression. Modulation of CSF-1 gene t ranscription by growth-arrest (decrease) or stimulation of growth-arre sted 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 (monocyte s) to determine if mechanisms used to control CSF-1 gene expression in fibroblasts are unique or represent common nontissue-specific regulat ory mechanisms. Analysis of CSF-1-CAT reporter constructs in transient ly transfected fibroblasts and monocytes was used to identify CSF-1 ge nomic sequences that affect transcriptional activity. DNase I protecti on, electrophoretic mobility shift, and methylation interference assay s were used to identify the putative cis-acting elements. Results of o ur study suggest multiple trans-acting factors may regulate CSF-1 gene expression; some may be tissue specific, while others, such as AP1, C TF/NF1, Spl, and Sp3, are shared in common. (C) 1997 Wiley-Liss, Inc.