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Human Epigenome Map Yields Insights into Development, Disease

Graphic representation of the massive amount of data from just one type of lung cell illustrates genome-wide measurements (X axis) from 127 reference genomes (Y axis) in 33 data sets (Z axis).Image by the researchers, courtesy of Nature

The sequencing of the human genome—the complete set of DNA in our cells—laid the foundation for understanding how variation in the genetic code can affect human health. The “epigenome” refers to the chemical modifications that affect how cells in different parts of the body use the same genome to form countless different types of cells and tissues. Epigenomic modifications don’t affect the DNA sequence itself. Rather, these alterations influence when specific genes are turned on and off, or “expressed.” These changes to DNA and its associated proteins tell cells what to do, where to do it, and when.

To gain a systematic understanding of how epigenomics contributes to human biology and disease, hundreds of researchers in labs around the world generated and analyzed over 100 reference human epigenomes from a broad range of cells and tissues. This is the largest collection to date of reference human epigenomes. The work was supported by the NIH Common Fund’s Roadmap Epigenomics Program. An overview of the effort was published on February 19, 2015, in Nature. More than 20 additional papers in Nature and Nature-associated journals showed how this information can be used to gain insights into human biology.

The researchers examined several types of epigenomic factors. These included DNA methylation (when chemical tags called methyl groups are attached to DNA directly), histone modifications (when methyl or acetyl groups are added to specific spots on histones, the proteins that package DNA), gene expression levels, and more.

This extensive resource will help scientists understand how epigenomic elements regulate gene expression to create different cell types and tissues, guide human development, and affect disease. Among the companion papers were epigenomic explorations that deepen our understanding of autoimmune disorders, Alzheimer’s disease, and cancer.

“What the Roadmap Epigenomics Program has delivered is a way to look at the human genome in its living, breathing nature from cell type to cell type,” says senior author Dr. Manolis Kellis at the Massachusetts Institute of Technology.

“Today, sequencing the human genome can be done rapidly and cheaply, but interpreting the genome remains a challenge,” says Dr. Bing Ren at the University of California, San Diego, co-author of the Nature paper and several of the associated papers. “These maps are like snapshots of the human genome in action.” 

All the data sets, standards, and protocols are publicly available through Web portals as a resource to spur future research. In addition to helping scientists understand how epigenomics affects human health and disease, this resource can be used to develop better ways to identify early signs of disease and targets for therapeutics.

—by Harrison Wein, Ph.D.