Each of the 200 or so different types of cells in our body—in the brain, the liver, the fat tissues—is handed the same basic instruction manual, yet somehow they all "see" a different set of instructions inscribed in the roughly 3 billion bases that make up the human genome. But it is the epigenome—a second layer of control beyond the regulation inherent in the sequence of the genes themselves—that controls which genes are accessible and when.
Some have compared it to the software run on the genomic hardware. "I can load Windows, if I want, on my Mac," says Joseph Ecker, professor and director of the Genomic Analysis Laboratory and a member of the San Diego Epigenome Center. "You're going to have the same chip in there, the same genome, but different software. And the outcome is a different cell type."
In a study "TIME" magazine recently ranked the second most important scientific discovery of 2009, Ecker and his team recently provided the first detailed map of the human genome.
"In the past we've been limited to viewing small snippets of the epigenome," says senior author Joseph Ecker. "Being able to study the epigenome in its entirety will lead to a better understanding of how genome function is regulated in health and disease but also how gene expression is influenced by diet and the environment."
Their study, published in the Oct. 14 advance online edition of Nature, compared the epigenomes of human embryonic stem cells and differentiated connective cells from the lung called fibroblasts, revealing a highly dynamic, yet tightly controlled, landscape of chemical signposts known as methyl-groups. The head-to-head comparison brought to light a novel DNA methylation pattern unique to stem cells, which may explain how stem cells establish and maintain their pluripotent state, the researchers say.
The emergence of epigenetics has already changed the way researchers think about how disease arises and how physicians treat it. Epigenetic changes play a crucial role in the development of cancer and some drugs that directly interact with the epigenome have been approved for the treatment of lymphoma and lung cancer and are now tested against a number of other cancer types.
"Unless we know how these drugs affect the entire epigenome, we don't really understand their full mechanism of action," says Ecker.
Recognizing the central role of the epigenome in many areas of biology and medicine, the National Institutes of Health launched a five-year Roadmap Epigenomics Program in 2008. The San Diego Epigenome Center, headed by Bing Ren, professor of Cellular and Molecular Medicine at the University of California, San Diego School of Medicine and head of the Laboratory of Gene Regulation at the Ludwig Institute for Cancer Research, is an integral part of the five year, $190 million push to accelerate research into modifications that alter genetic behavior across the human genome.