Published online 6 October 2010 | Nature 467, 646 (2010) | doi:10.1038/467646a
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Epigenome effort makes its mark
Major release of maps charting non-genetic modifications goes beyond DNA in a bid to beat complex human disease.
Alla Katsnelson
When the human genome was first fully sequenced, it was often described as the recipe for making a person. In reality, the genome is more like an entire cookbook that can produce hundreds of different cell types and a staggering range of cell functions depending on which genes are switched on and off. That switching is accomplished using a vast suite of epigenetic marks — molecular and structural modifications to DNA that do not change the underlying sequence but ensure that the right genes are expressed at the right time.
This week, the Roadmap Epigenomics Project, a US$170-million effort to identify and map those marks — known collectively as the human epigenome — begins its first comprehensive data release. Although it is not the only such effort worldwide (see Nature 463, 596–597; 2010), the US National Institutes of Health (NIH) epigenomics project is one of the most ambitious. The newly released data include more than 300 maps of epigenetic changes in 56 cell and tissue types, and represent a significant step towards the complete epigenome — the full picture of all the ways in which DNA can be modified, thus revealing the influence of epigenetics on cell development and its role in complex diseases (see graphic).
Various epigenetic mechanisms regulate gene expression. These include different types of modification on the histone proteins around which genomic DNA winds; attachment of methyl groups to the nucleotide cytosine in DNA, an alteration that is thought to switch off genes; sites of high sensitivity to an enzyme called DNase I, which cleaves accessible DNA and marks the location of gene regulatory regions; and RNA transcription, which, although not a DNA mark, is one measure of the global epigenetic state, revealing how much protein a particular gene makes in different cells. The NIH project developed a standardized protocol for measuring these four factors, and four designated centres around the United States have been charged with making reference maps of each type of modification in embryonic stem cells, induced pluripotent cells and in hundreds of primary adult and fetal tissues.
The project, slated to run for another five years, aims to produce maps for "a broad swathe of cell types that would be useful to disease research, fund work on specific diseases and develop novel technologies," says John Satterlee, a behavioural geneticist at the National Institute on Drug Abuse in Rockville, Maryland, and one of the coordinators of the project.
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