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Biological Chemistry

Genome Changes Mapped In Humans

Epigenomics: Most comprehensive results to date in collaborative epigenome-mapping project

by Stu Borman
February 19, 2015 | APPEARED IN VOLUME 93, ISSUE 8

Researchers reported last week that a DNA-methylation gene called uhrf1 is a molecular trigger for inflammatory bowel disease (Proc. Natl. Acad. Sci. USA 2015, DOI: 10.1073/pnas.1424089112). It was already known that immunity and genetics play a role in the disease. “But we’ve found that it is not just the immune genes themselves but also the regulation of those genes through epigenetics that can cause problems,” says corresponding author and Duke University cell biologist Michel Bagnat.

The finding is just one example of the importance of epigenetics, or epigenomics—the study of how modifications to a cell’s genome can influence human development, health, and disease. If a series of studies published last week in Nature and several other Nature research journals are any indication, there will be many more such examples to come (http://nature.com/epigenomeroadmap).

The studies report the most comprehensive results to date from the Roadmap Epigenomics Project, the epigenomics version of the Human Genome Project.

All the nongerm cells in a particular organism are genetically identical, but not all genes get expressed the same way across cell types. Such variations in gene expression are what differentiate embryonic from adult cells, heart from brain cells, and normal from diseased cells. The epigenomic factors that control differential gene expression include methylation of specific DNA bases, chemical modifications to the proteins called histones that package eukaryotic DNA, and DNA conformation changes that promote the binding of regulatory transcription factors.

Researchers in the Roadmap Epigenomics Project—an international collaboration sponsored by the National Institutes of Health—have now mapped the epigenomes of more than 100 human cell types and report on how epigenomics affects diseases such as cancer and Alzheimer’s, differentiation of stem cells into adult cells, and other biological functions.

In a Nature commentary, molecular biologist Hendrik G. Stunnenberg of Radboud University, in the Netherlands, says that the community now “plans to determine the epigenomes of every cell type in the human body—estimated to be several hundred to 1,000.”

09308-notw4-roadmap_19945349-690.jpg
Credit: John Stamatoyannopoulos & Rae Senarighi
Key factors that affect gene expression include DNA methylation, chemical modifications to histones, and conformational changes that attract gene-regulating transcription factors (colored shapes).
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