Researchers at the Broad Institute of Harvard and MIT announced Sept. 30 that they have received a grant from the National Institutes of Health (NIH) to map the epigenomes of a variety of medically important cell types, including human embryonic stem cells.
The five-year, $15 million grant, part of the NIH Roadmap for Medical Research, designates the institute as one of four Reference Epigenome Mapping Centers (REMC) nationwide that will aim to transform the understanding of an exquisite control system — a code of so-called epigenetic cues that specify when and where in the body genes are made active. To systematically decipher and analyze these controls, researchers from across the Harvard and MIT communities will come together to study at least 100 distinct types of human cells using the latest methods in stem cell biology, genomics, technology, computation, and production-scale research.
“The human epigenome is arguably the next frontier of genomic research,” said co-principal investigator Alex Meissner, who is an associate member at the Broad Institute and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “Bolstered by recent technological advances, this award will enable us to create comprehensive epigenomic maps of a variety of human cells and to share that data with the worldwide scientific community.”
“Epigenomics lies at a key intersection point between genome biology and human disease,” said Bradley Bernstein, a co-principal investigator as well as a Broad Institute associate member and an assistant professor at Harvard Medical School and Massachusetts General Hospital. “By glimpsing the normal epigenome at unprecedented breadth and depth, we will lay the critical groundwork for future insights into the epigenetic basis of a variety of diseases, including cancers.”
An overarching question in human biology is how cells in the body, with the exact same DNA, adopt such distinct forms and functions. The answer lies mainly in the epigenome, a special code of chemical tags affixed to DNA or to its supporting proteins (known as “histones”) that act as gatekeepers to the genome — enabling genes to be switched on or ensuring they remain switched off. In the past few years, two techniques have transformed researchers’ abilities to probe cells’ epigenomes: ChIP-Seq and high-throughput bisulfite sequencing (HTBS). These technologies can help pinpoint the genomic locations of various types of chemical tags, such as methyl groups, and thus chart the epigenome.
REMC at the Broad Institute will help create comprehensive, genome-scale maps of the epigenomes of a variety of cells, including human embryonic stem cells, various adult stem cells, and other key cell types. The researchers will survey both the DNA backbone and its accompanying histone proteins for chemical modifications using HTBS and ChIP-Seq, respectively, which take advantage of the increased throughput and decreased cost of next-generation DNA sequencing, and provide unprecedented precision and genomic coverage.
Just as the Human Genome Project provided researchers with a draft genome sequence, the REMCs will help create draft epigenomic maps of a diverse set of cell types. Those data will serve as a vast resource for the scientific community to enhance the understanding of epigenetic mechanisms of disease, pinpoint novel molecular targets for therapy, complement ongoing investigations of the genetic susceptibilities of a wide range of diseases, and bolster current research in stem cell biology and regenerative medicine.
The NIH award to the Broad Institute represents one of four areas of epigenomic research to receive funding under the NIH Roadmap Epigenomics Program. In addition to the work of the epigenome mapping centers, other funded centers will focus on epigenomics data analysis and coordination, technology development in epigenetics, and the discovery of novel chemical tags that mark the epigenomes of mammalian cells.