VISTA Enhancer Browser--a database of tissue-specific human enhancers

Abstract

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.

Figure 1

Display of experimental results for an element with reproducible enhancer activity. Flanking gene(s) are indicated at the top of the page (white arrow). The expression pattern is described by standardized anatomical terms (yellow arrow) and images of representative embryos (green arrow) are shown above the sequence of the tested human element (blue arrow) and its conservation profile (red arrow). All embryo pictures can also be viewed at high resolution (inset).

Figure 2

Retrieving enhancers that drive reporter gene expression to a user-defined anatomical structure, in this case forebrain. (A) Each row in the results table corresponds to one in vivo-assayed element. A mouse icon (blue) indicates that an element is an enhancer at E11.5. Pufferfish, zebrafish, chicken and frog icons indicate the conservation depth of the element. Images of representative embryos for each dataset (B) and more detailed information about the conservation profile of the respective element can be obtained by following the ‘location’ link.