Editing the epigenome

What: In continued work of the ENCODE project, which is aimed at uncovering the functional landscape of the human genome, a team of researchers from the Broad Institute’s Epigenomics Program and the Massachusetts General Hospital recently developed a method to test the functions of genomic elements.

The method targets suspected enhancers – “switches” that control the activity of nearby genes – by homing in on their signature epigenomic (i.e., “on top of the genome”) marks.

“Work by ENCODE and the Epigenomics consortium has identified many thousands of putative enhancers in the human genome,” said Brad Bernstein, lead author on the work, senior associate member at the Broad Institute, and associate professor of pathology at Massachusetts General Hospital (MGH) and Harvard Medical School. “Yet for the vast majority of these elements, it remains unclear what, if anything, they do.”

The team developed a system that takes advantage of programmable proteins, known as TAL effectors, that can zero in on specific areas of the genome. By fusing these TAL effectors to enzymes, they created an experimental tool that can home in on suspected genomic switches and inactivate them. Using this tool, they identified a handful of genes that were “turned down” by this process, confirming the functional role of suspected enhancers and revealing their regulatory targets.

Who: A team of scientists from the Broad Institute, Massachusetts General Hospital, Harvard Medical School, Harvard University, and Howard Hughes Medical Institute. Broad contributors include Eric Mendenhall (first author), Kaylyn Williamson, James Zou, Oren Ram, and Bradley Bernstein (senior author).

Why: Earlier phases of the ENCODE project resulted in a map of epigenomic marks, suggesting the locations of genetic switches, but not their gene targets.

With this tool in hand, the researchers now have a path towards generating a more complete epigenomic map, with information on how the switches regulate genes. Understanding how these elements are wired and connected remains a key goal of Bernstein’s lab and others in the Epigenomics Program.

The approach may also allow disease-associated genes to be regulated by inactivating their switches, and thus guide new therapeutic strategies.

Where to find it: Nature Biotechnology