It’s amazing to think that we all started out as one cell with DNA from our parents inside. Now, researchers in Spain and the Netherlands say that they have a better idea of how development happens—and enhancers are showing them the way by pointing out active genes.
The researchers knew that active enhancers are marked by histone modifications H3K4me1 and H3K27ac, but little was known regarding how many of these histone modifications are active or what they are actually doing during vertebrate embryogenesis. To figure this out, they produced genome maps of H3K4me1 (and H3K4me3) and H3K27ac at four developmental time points during zebrafish development using ChIP-seq. They call their enhancer collections putative distal regulatory elements (PDREs). Here’s what they learned:
- H3K4me1 and H3K27ac marks correlate well with the timing of gene expression. Sometimes, the enhancer marks appear even before transcriptional activation (as marked by H3K4me3).
- The earliest stage (blastula) had the fewest PDREs.
- There’s lots of gene expression going on from blastula to the gastrula stage, and maybe not-so-coincidentally, the most conserved PDREs are those that are turned on during that transition.
- Lots of developmental genes have PDREs.
- H3K27ac is more dynamic than H3K4me1. In fact, the findings suggest that H3K27ac marks the transition to a more differentiated state.
- Most regions with H3K4me1 and H3K27ac are associated with enhancers, though one-third of those they tested didn’t act like enhancers in an assay.
- H3K4me1 mark appears before H3K27ac at several locations. These might be “poised” enhancers.
The team says that H3K27ac deposition and removal at enhancers could “constitute an essential mechanism for the transition of pluripotency to cell differentiation.”
Read the developments at Genome Research, May 2012.