In Once-Mysterious Epigenome, Scientists Find What Turns Genes On

Over a decade ago, the Human Genome Project deciphered the “human instruction book” of our DNA, but how cells develop vastly different functions using the same genetic instructional text has remained largely a mystery.

As of yesterday, it became a bit less mysterious. A massive NIH consortium called the Roadmap Epigenomics Program published eight papers in the journal Nature which report on their efforts to map epigenetic modifications, or the changes to DNA that don’t alter its code. These subtle modifications make genes more or less likely to be expressed, and the collection of epigenetic modifications is called the epigenome.

A handful of new studies provide epigenetic roadmaps to understanding the human genome in action.

One of the eight studies mapped over 100 epigenomes characterizing every epigenetic modification occurring in human tissue cells. “These 111 reference epigenome maps are essentially a vocabulary book that helps us decipher each DNA segment in distinct cell and tissue types,” Roadmap researcher Bing Ren, a professor of cellular and molecular medicine at the University of California, San Diego, said in a news release. “These maps are like snapshots of the human genome in action.”

This kind of mapping has challenged the field because of the huge amount of data needed to make sense of the chaotic arrangements of genes and their regulators. “The genome hasn’t nicely arranged the regulatory elements to be cheek by jowl with the elements they regulate,” Broad Institute director Eric Lander told Gina Kolata at The New York Times. “It can be very hard to figure out which regulator lines up with which genes.”

Here’s how Lander described the detective process used to Kolata:

If you knew when service on the Red Line was disrupted and when various employees were late for work, you might be able to infer which employees lived on the Red Line, he said. Likewise, when a genetic circuit was shut down, certain genes would be turned off. That would indicate that those genes were connected, like the employees who were late to work when the Red Line shut down.

Diseases can be linked to epigenetic variations as well. For example, another of the eight papers published yesterday proposed that the roots of Alzheimer’s disease lie in immune cell genetic dysfunction and epigenetic alterations in brain cells.

Creating an epigenetic road map is a huge step, but it’s just a first step. As Collins wrote in 2001 when the human genome had been mostly mapped, “This is not even the beginning of the end. But it may be the end of the beginning.”