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) 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 I 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, Sp1, and Sp3, are shared in common.
Harrington
M
M
Indiana University, Indianapolis 46202, USA.
Konicek
B W
BW
Xia
X L
XL
Song
A
A
D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016173:Macrophage Colony-Stimulating Factor