A conserved upstream element in the mouse Csf1r locus contributes to transcription in hematopoietic and trophoblast cells.

Expression of the Csf1r gene in mice is restricted to cells of the mononuclear phagocyte system and placental trophoblasts. A conserved element (Csf1r upstream regulatory element A [CUREA]) in the mouse Csf1r locus contains transcription start sites utilized by trophoblasts and osteoclasts and an enhancer essential for expression of multicopy transgenic reporters in most tissue macrophages. Here, we describe the impact of deletion of CUREA in the mouse genome on the background of a knock-in Csf1r-FusionRed reporter. By contrast to the essential function in transgene expression, CUREA deletion had no effect on expression of FusionRed or differentiation of blood monocytes or tissue resident macrophages. The deletion reduced Csf1r messenger RNA in hematopoietic stem cells and committed myeloid progenitors (MPP3), leading to a subtle differentiation delay, and had a significant impact on microglial density in the brain and the differentiation of osteoclasts. The expression of FusionRed in placenta confirmed expression of CSF1R in trophoblasts. 5'RACE analysis demonstrated that the effect of CUREA deletion on Csf1r transcription in placenta was overcome by the use of cryptic upstream transcription start sites. We conclude that CUREA is a regulatory element controlling Csf1r transcription. The function overlaps with other enhancers identified in the locus and is therefore partly redundant.