Joseph Costello, Ph.D.; Bradley Berstein, M.D., Ph.D.; Alexander Meissner, Ph.D.; John Stamatoyannopoulos, M.D.; Bing Ren, Ph.D.
University of California, San Francisco; Broad Institute, Inc.; University of Washington, Ludwig Institute for Cancer Research, Ltd.
NIEHS Grants U01ES017154, U01ES017155, U01ES017156
Researchers supported by the NIH Common Fund’s Roadmap Epigenomics Program, which is co-led by NIEHS, have mapped the epigenomes of more than 100 types of human cells and tissues. This information can help scientists find out how changes to the genome and epigenome can lead to conditions such as Alzheimer’s disease, cancer, asthma, and fetal growth abnormalities.
Epigenetic changes are chemical modifications to DNA that alter how genes are expressed without changing the genetic code. The epigenome contributes to unique gene expression and biological functions, and thus, unlike the genome, can vary among cells and tissues. To better understand how the epigenomic landscape contributes to cell function and differentiation as well as human disease, the researchers integrated information about histone marks, DNA methylation, DNA accessibility, and RNA expression to produce high-resolution maps of gene regulatory elements across 127 — 111 from the Roadmap Epigenomics Program and 16 from the Encyclopedia of DNA Elements project — reference epigenomes from a diverse group of cell and tissue types.
The resulting comprehensive catalog of epigenomic data provides a first-of-its kind resource for researchers to make direct comparisons across cell types and tissues. The researchers expect the data, which is freely available, will be of broad use to scientists for studies of gene regulation, cellular differentiation, genome evolution, genetic variation, and human disease. More than 20 additional papers, published in Nature and Nature-associated journals, show how these maps can be used to study human biology.
Citation: Roadmap Epigenomics Consortium, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller MJ, Amin V, Whitaker JW, Schultz MD, Ward LD, Sarkar A, Quon G, Sandstrom RS, Eaton ML, Wu YC, Pfenning AR, Wang X, Claussnitzer M, Liu Y, Coarfa C, Harris RA, Shoresh N, Epstein CB, Gjoneska E, Leung D, Xie W, Hawkins RD, Lister R, Hong C, Gascard P, Mungall AJ, Moore R, Chuah E, Tam A, Canfield TK, Hansen RS, Kaul R, Sabo PJ, Bansal MS, Carles A, Dixon JR, Farh KH, Feizi S, Karlic R, Kim AR, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer TR, Neph SJ, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari RC, Siebenthall KT, Sinnott-Armstrong NA, Stevens M, Thurman RE, Wu J, Zhang B, Zhou X, Beaudet AE, Boyer LA, De Jager PL, Farnham PJ, Fisher SJ, Haussler D, Jones SJ, Li W, Marra MA, McManus MT, Sunyaev S, Thomson JA, Tlsty TD, Tsai LH, Wang W, Waterland RA, Zhang MQ, Chadwick LH, Bernstein BE, Costello JF, Ecker JR, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos JA, Wang T, Kellis M. Integrative analysis of 111 reference human epigenomes. 2015. Nature 518(7539):317-330.