Enhancer regions are starting to come into their own as important members of the epigenome – way more than just add-ons that increase promoter transcription. A new study shows us that the RNA world just won’t stop expanding. Drs. Rao and Yuan from the Blood Center of Wisconsin and Harvard, along with a talented team of researchers, have given us an enhanced view of the latest world to emerge; a novel epigenetic signature that identifies enhancer transcribed RNAs (eRNAs) based on DNA hypomethylation and Tet-occupation.

Drs. Rao and Yuan share that; “While hypomethylation is known to correlate with promoter transcription, enhancers were previously thought to show an intermediate level of DNA methylation.” In their work they “thoroughly investigated the association between eRNA productivity and various chromatin marks and transcriptional regulators in mouse embryonic stem cells (ESCs) through an integrative approach.”

Here’s what they found:

“Highly active enhancers, which produce eRNAs, show very low levels of DNA methylation.”

This also closely correlated with “Tet1 occupancy, further implying that regulation of DNA methylation is important to enhancer activity.”

Interestingly, “These same enhancers also correspond to pluripotency-associated genes, indicating they are likely central to regulating Embryonic Stem Cells (ESCs)” and seem to have crucial developmental functions, as illustrated by the example of their investigation into “a well characterized enhancer linked to the Nanog locus”, which they showed exclusively produces eRNAs in ESCs.

Rao and Yuan shared their surprise “that enhancer and promoter transcription did not seem to correlate.” This implied to them “that the presence of enhancer transcription, but not the degree, mark these regions as active enhancers, suggesting a multi-step process on gene activities.” They also share that “to a large extent,” these finding “dispels the notion that enhancer transcription is simply a by-product of an extremely active promoter.”

Rao and Yuan also shared their perspective that since “The vast majority of the transcribed genome does not code for proteins, we are still at the early stage of understanding the function of these noncoding RNA. This will likely have profound impact on how we understand the meaning of genes and the role of genetic variation in human diseases. Our work demonstrates that transcribed enhancers are a highly active subset of lineage-specific cis-regulatory elements. In addition, it highlights the importance of DNA demethylation machinery in enhancer function.”

Enhance your view of the RNA world over at Epigenetics, October 2013