Broad epigenetics research makes a big splash

Leah Eisenstadt, September 29th, 2010 | Filed under

According to some, epigenomics is the next frontier for genome researchers. Literally meaning “on top of” the genome, the epigenome refers to chemical tags that attach to DNA and the protein scaffold that supports it, together known as “chromatin.” Those tags help turn genes on and off, and therefore they can have huge biological implications.

Researchers in the Broad Institute’s Epigenomics Initiative work to understand how the epigenetic modifications to chromatin can affect human health. But they can’t chart a course for discovery without a good map. Therefore, one of the main research aims of the team is to generate good maps of chromatin changes in lots of different cell types, such as stem cells and cancer cells.

In 2008, using enhanced mapping techniques that harness the technological power of sequencing, Broad scientists analyzed DNA methylation — one common form of epigenetic modification — across the genomes of embryonic stem cells. The first-of-their-kind maps have since helped scientists across the globe pursue questions like how epigenetic factors influence cell development. The work originally appeared online in Nature in July 2008, and Nature Biotechnology has deemed it the most cited publication in the field of epigenetics during 2009, with 211 other papers citing it. The research team was led by Broad director Eric Lander, associate member Alexander Meissner, and Tarjei Mikkelsen (then a graduate student in Eric Lander’s group).

Most recently, Meissner and his fellow researchers have compared four approaches to mapping DNA methylation on a genomic scale, including the bisulfate sequencing method they used to create the influential 2008 map. Their analysis revealed that the four methods all produce accurate DNA methylation data, but differ in the ability to detect regions that are methylated differently in pairs of cell samples, such as two human embryonic stem cell lines and a pair of colon tumor and normal colon tissue from the same donor.

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