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The Bone Morphogenetic Protein (BMP) pathway is a multi-member signaling cascade whose basic components are found in all animals. One member, BMP3, which arose more recently in evolution and is found only in deuterostomes, serves a unique role as an antagonist to both the canonical BMP and Activin pathways. However, the mechanisms that control BMP3 expression, and the  cis -regulatory regions mediating this regulation, remain poorly defined. With this in mind, we sought to identify the  Bmp3  promoter in mouse  (M. musculus ) through functional and comparative genomic analyses. We found that the minimal promoter required for expression in resides within 0.8 kb upstream of  Bmp3  in a region that is highly conserved with rat ( R. norvegicus ). We also found that an upstream region abutting the minimal promoter acts as a repressor of the minimal promoter in HEK293T cells and osteoblasts. Strikingly, a portion of this region is conserved among all available eutherian mammal genomes (47/47), but not in any non-eutherian animal (0/136). We also identified multiple conserved transcription factor binding sites in the  Bmp3  upstream ECR, suggesting that this region may preserve common  cis -regulatory elements that govern  Bmp3  expression across eutherian mammals. Since dysregulation of BMP signaling appears to play a role in human health and disease, our findings may have application in the development of novel therapeutics aimed at modulating BMP signaling in humans.

Comparative Genomics Identifies the Mouse Bmp3 Promoter and an Upstream Evolutionary Conserved Region (ECR) in Mammals