Randazzo F M, Khavari P, Crabtree G, Tamkun J, Rossant J
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Dev Biol. 1994 Jan;161(1):229-42. doi: 10.1006/dbio.1994.1023.
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.
为了鉴定小鼠中Hox基因表达的潜在调节因子,我们筛选了与果蝇同源异型基因表达激活因子brahma(brm)高度相关的基因。我们克隆了一个小鼠基因brg1,它与brm一样,编码DEGH蛋白家族的一个成员,这表明brg1可能是一种依赖DNA的ATP酶或解旋酶。brg1还包含一个可能参与反式激活的溴结构域。虽然已经报道了一些与果蝇brm相似的哺乳动物基因序列,但它们仅在假定解旋酶区域的特定部分与brm相关,而brg1在该区域内外都与brm高度相似。在整个胚胎发育过程以及许多成年组织中都检测到了一个5.8kb的brg1转录本。RNA原位杂交显示brg1在胚胎组织中广泛表达。在胚胎发育的后期阶段,不同组织中brg1的表达水平存在差异。brg1在脊髓、脑、部分外周神经系统和脊柱中的表达最高。脊髓和脊柱内的这些表达区域涵盖了Hox基因表达的主要区域。在脊髓、脑和视网膜内,由分化细胞组成的区域中的mRNA水平高于由未分化的增殖细胞组成的区域。brg1的这些表达模式与brg1在Hox基因调控以及其他调控途径中可能发挥的作用相一致。