Searching for functional enhancers is sort of like panning for gold; there is enormous potential for riches, but the task is akin to finding a needle in a stack of needles. A team from the Berkeley National Laboratory decided to apply their own gold rush-style, enhancer mining techniques to develop a new method for the discovery of functional enhancers aided by some clever cross species stem cell epigenomics. Here’s what the mining operation unearthed:
- Trading sifting pans for NGS and ChIP, the team developed site-specific integration fluorescence-activated cell sorting followed by sequencing (SIF-seq).
- Using reporter assays in mouse embryonic stem cells, the technique can identify human embryonic stem cell enhancers that are not present in the mouse genome.
- Showing off the techniques true grit, the team identified enhancers at mouse and human pluripotency loci, including the famous NANOG.
- The technique also demonstrated that it can be used to find cell-type specific enhancers in differentiated cardiomyocytes and neural progenitor cells (in vitro).
Overall, SIF-seq proved to be a powerful and flexible new technique for the de novo functional enhancer identification. It has the potential to be used for discovery in a number of unexplored cell types and developmental contexts given its cross species abilites. When it comes to application, Lead Author Diane Deckel shares her outlook that “SIF-seq is currently capable of testing only hundreds to a few thousand sites for enhancer activity in a single experiment, but can determine enhancer activity more accurately than ChIP-seq and is therefore a very good validation assay for assessing ChIP-seq results.”
Learn how to sift for your genomic gold over at Nature Methods, April 2014