Visel Axel, Minovitsky Simon, Dubchak Inna, Pennacchio Len A
Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 USA.
Nucleic Acids Res. 2007 Jan;35(Database issue):D88-92. doi: 10.1093/nar/gkl822. Epub 2006 Nov 27.
Despite the known existence of distant-acting cis-regulatory elements in the human genome, only a small fraction of these elements has been identified and experimentally characterized in vivo. This paucity of enhancer collections with defined activities has thus hindered computational approaches for the genome-wide prediction of enhancers and their functions. To fill this void, we utilize comparative genome analysis to identify candidate enhancer elements in the human genome coupled with the experimental determination of their in vivo enhancer activity in transgenic mice [L. A. Pennacchio et al. (2006) Nature, in press]. These data are available through the VISTA Enhancer Browser (http://enhancer.lbl.gov). This growing database currently contains over 250 experimentally tested DNA fragments, of which more than 100 have been validated as tissue-specific enhancers. For each positive enhancer, we provide digital images of whole-mount embryo staining at embryonic day 11.5 and an anatomical description of the reporter gene expression pattern. Users can retrieve elements near single genes of interest, search for enhancers that target reporter gene expression to a particular tissue, or download entire collections of enhancers with a defined tissue specificity or conservation depth. These experimentally validated training sets are expected to provide a basis for a wide range of downstream computational and functional studies of enhancer function.
尽管人类基因组中存在已知的远距离作用顺式调控元件,但其中只有一小部分在体内被鉴定并进行了实验表征。因此,缺乏具有明确活性的增强子集合阻碍了全基因组范围内增强子及其功能预测的计算方法。为了填补这一空白,我们利用比较基因组分析来识别人类基因组中的候选增强子元件,并结合在转基因小鼠中对其体内增强子活性的实验测定[L. A. Pennacchio等人(2006年),《自然》,即将发表]。这些数据可通过VISTA增强子浏览器(http://enhancer.lbl.gov)获取。这个不断增长的数据库目前包含超过250个经过实验测试的DNA片段,其中100多个已被验证为组织特异性增强子。对于每个阳性增强子,我们提供了胚胎第11.5天的全胚胎染色数字图像以及报告基因表达模式的解剖学描述。用户可以检索感兴趣的单个基因附近的元件,搜索将报告基因表达靶向特定组织的增强子,或下载具有定义的组织特异性或保守深度的增强子完整集合。这些经过实验验证的训练集有望为增强子功能的广泛下游计算和功能研究提供基础。