To identify potential regulators of Hox gene expression in mice, we have screened for genes highly related to brahma (brm), an activator of homeotic gene expression in Drosophila. We have cloned a murine gene, brg1, which, like brm, encodes a member of the DEGH protein family, suggesting that brg1 may be a DNA-dependent ATPase or a helicase. brg1 also contains a bromodomain which may be involved in transactivation. Although the sequences of a number of mammalian genes similar to Drosophila brm have been reported, they are related to brm only within specific portions of the putative helicase region, while brg1 is highly similar to brm throughout and outside of this region. A 5.8-kb brg1 transcript was detected throughout embryogenesis and in numerous adult tissues. RNA in situ hybridization revealed widespread expression of brg1 in embryonic tissues. At later stages of embryogenesis, differences in levels of brg1 expression were seen among different tissues. brg1 expression was highest in the spinal cord, the brain, parts of the peripheral nervous system, and the vertebral column. These expression domains within the spinal cord and vertebral column encompass major regions of Hox gene expression. Within the spinal cord, brain, and retina, mRNA levels were higher in regions consisting of differentiated cells than in regions consisting of undifferentiated, proliferating cells. These patterns of brg1 expression are consistent with a possible role for brg1 in Hox gene regulation as well as in other regulatory pathways.