The VISTA tools for comparative genomics are really nice to compare sequences across species–we’ll have a tip about that soon. But in addition to the tools that do these comparisons, which are the main focus of our full tutorial , there is another data set available from this team. The work on the VISTA Enhancer Browser demonstrates that the knowledge you can derive from the computational analyses can go into the lab to yield some new insights into the role of possible regulatory regions. This quick clip introduces the concept and shows a bit of data (~4min).
We have a lot to learn about regulatory regions–enhancers, promoters, etc. The goal of this project was to find certain non-coding regions that are highly conserved between species and see if they correspond to interesting expression patterns in mouse embryos. This provides useful information about the regulation of certain genes based on these possible enhancers, and also offers useful “computational reagents” in the form of validated sequence sets that could be used for other types of computational studies as well.
At the time they wrote their paper on this, there were about 250 segments tested, with about 100 demonstrating positive expression in certain tissues. As of today there have been nearly 750 segments tested and 321 of those with positive expression of reporter constructs. You can look at them by region, or by tissue expression pattern, or several other ways.
You can even find those that are reported as negative expression for the construct. It is impossible to know if that is negative because of experimental artifacts or technical issues, or it could be a temporal issue–an enhancer earlier or later in development, or under some other condition besides embryonic development there could be some activity there–for example during infection or wounding or some other physiological state . I guess they could be another kind of regulatory region–such as repressors–as well.
It is an interesting way to take that genome-wide computational data analysis and translate it to the bench. And it is even a case where the negative data could be a useful starting point for other pursuits.
Visel, A., Minovitsky, S., Dubchak, I., Pennacchio, L.A. (2007). VISTA Enhancer Browser–a database of tissue-specific human enhancers. Nucleic Acids Research, 35(Database), D88-D92. DOI: 10.1093/nar/gkl822