Transcriptional effects of colony-stimulating factor-1 in mouse macrophages

Colony-stimulating factor-1 (CSF-1) is a major regulator of macrophage development. CSF-1-dependent signalling has been implicated in proliferation, survival, and differentiation of mononuclear phagocytes, however, relatively little is known about the effects of CSF-1 on macrophage gene transcription and on CSF-1-responsive gene promoters. We used a combination of transcription profiling and in silico motif search to characterize genes that are regulated in mature bone marrow-derived macrophages cultured in the presence or absence of CSF-1. The expression of many known differentiation-associated macrophage markers was not significantly affected in the absence of CSF-1. Genes repressed by CSF-1 comprised a considerable number of granulocyte-specific genes. The respective gene promoters; however, were not significantly enriched for specific DNA patterns, suggesting that these genes are regulated by promoter-distal elements or at a post-transcriptional level. Genes downregulated upon CSF-1 deprivation showed a highly significant association with cell division which is in line with the known role of CSF-1 as a proliferation stimulus for mouse macrophages. Interestingly, three DNA patterns were significantly co-enriched in CSF-1-dependent gene promoters, including motifs related to NFY, CHR, and E2F sites. These motifs showed a strong positional preference on target promoters at -60, -30 and 0 bp upstream of the transcription start site, and define the common promoter structure of CSF-1-responsive genes.