A detailed new map of our genome in action

Each cell in your body has the same DNA, but they don’t all follow the same instructions. Some become blood cells; others become brain cells or muscle tissue. But if the DNA has a mistake or the cells turn on the wrong set of genes, that can lead to disease.

So how do cells decide which genes to turn on and which to turn off in different tissues? That’s the basis of epigenomics, chemical markers on the DNA and its packaging. Epigenomics is the focus of this week’s issue of the journal Nature, which includes a collection of papers from the Roadmap Epigenomics Program, a reference map of these modifications across a variety of human cells built by an international collaboration of scientists and researchers. Eight papers from the project are featured this week’s issue of Nature, and 16 others are published this week in other Nature journals.

“The genome contains all these genes, but it doesn’t tell you anything about how they’re working. These maps are giving snapshots of the genome in action,” said Lisa Helbling Chadwick, Roadmap Epigenomics Program team leader and program director at the National Institute of Environmental Health Sciences. “Our cells all have the same instruction book, but they have very different functions. How do they take this one set of instructions and come out so different?”

Think of it this way, said Manolis Kellis, professor of computer science at MIT and author of several of the papers on the issue: You start as a single cell, a zygote with a 6.5 foot-long string of DNA with billions of letters. That genetic material contains all the instructions from mom and dad that you’ll need throughout your lifetime. But you don’t need it all at once.

Enter the epigenome. Think of the epigenome, Kellis said, as a set of color-coded Post-It notes stuck to that DNA. These Post-Its are chemical modifications that can be read by different proteins and control how the DNA is getting used.

So continuing this analogy, green Post-It notes might point to the genes that are on, and yellow notes might point to the genes that are off. Orange notes might point to the control switches that help turn these genes on and off.

“All cells in our body contain a copy of the same genome, the ‘book of life’ that we inherited from our parents. However, each cell is using the book in a slightly different way. They’re all reading different chapters, bookmarking different pages, and highlighting different paragraphs and words,” Kellis said. “The human epigenome is this collection of marks placed on the genome in each cell type, in the form of chemical modifications on the DNA itself, and on the packaging that holds DNA together.”

The journal Nature explained it in musical terms:

On the surface, about 99.9 percent of our genome is the same from person to person, Kellis said. That still leaves .1 percent, or about 3 million letters that are different, scattered throughout all our genes. But it takes nature and nurture to make us who we are, he said. If DNA is the “nature” part of the equation, then epigenomics straddles the line between nature and nurture. Your genome was inherited, but your epigenome is partly shaped by environment and lifestyle.

Those changes to your epigenome could determine whether you’re more likely to get the flu each year, or whether you’re at risk to develop cancer. Your epigenome might even be responsible for some of your personal preferences, like whether you crave certain foods, or like math or history, Kellis said.

“That’s what’s really exciting about the epigenome,” Kellis said. “Maybe I was born in a very warm country, and you were born in a very cold country. Or maybe I was eating a lot of junk food and you were eating all veggies. That actually influences our epigenome.”

Since 2008, the Roadmap Epigenomics Program has been building a database of these modifications. Over the course of 2,800 experiments, scientists have profiled more than 100 cell and tissue types for the program. The mapping part of the project is over, but that alone has been a “major accomplishment,” Chadwick said.

Understanding how the epigenome works takes our understanding of disease to a new level, Chadwick said. Suddenly, genetic mutations that appeared to do nothing make sense when you understand how they relate to the epigenome, she said.

Scientists are already drawing connections between the epigenome and different diseases, like Type-1 diabetes, rheumatoid arthritis, cancer and multiple sclerosis. One of Kellis’ studies found that epigenome signals in immune cells play a role in Alzheimer’s disease.


The Human Genome Project gave us the full set of instructions for a complete human being, and the ten years that followed revealed thousands of genetic differences associated with human disease. The epigenomic maps released today can lead to new insights and treatments for disease. But there’s still a long way to go in this research, Kellis said.

“This is the most comprehensive map that we’ve built to date, but it’s nowhere near the end of the story for the epigenome,” Kellis said. “Understanding how our epigenome varies from individual to individual, and how it varies between disease and healthy conditions will be a long road ahead, but we now have a map that can guide us for years to come.”

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