Today Nature published an Integrative analysis of 111 reference human epigenomes in an open access article aimed at creating a reference collection of human epigenomes for primary cells and tissues as a resource analogous to the reference human genome. This is the largest collection so far, produced by the NIH Roadmap Epigenomics Consortium.
The NIH Roadmap Epigenomics Program was established with the goal of elucidating how epigenetic processes contribute to human biology and disease. To this end, the researchers have developed profiles for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. They have established global maps of regulatory elements and defined regulatory modules of coordinated activity and their likely activators and repressors. Disease- and trait-associated gene variants were found to be enriched in tissue-specific epigenomic marks, revealing relevant cell types for human traits, and providing a new resource for interpreting the molecular basis of human disease. Epigenetic differences underlie many challenges to precision medicine, such as variable penetrance and expressivity of genotypes known to contribute to “genetic” diseases, by influencing expression of encoded proteins and regulatory RNAs.
Methods used to develop these reference epigenomes include MethylC-seq, a 2-d protocol that enables the genome-wide identification of cytosine DNA methylation states at single-base resolution. Mark A Urich, Joseph R Nery, Ryan Lister, Robert J Schmitz and Joseph R Ecker of Howard Hughes Medical Institute and The Salk Institute, researchers of the NIH Roadmap Epigenomics Consortium, describe their MethylC-seq protocol in Nature Protocols. This specially designed protocol allows for the identification of DNA methylation features which are not readily apparent from traditional bisulfite-PCR methods, such as the identification of non-CG methylation in human embryonic stem cells and brain tissues, and the identification of large partially methylated domains in animal genomes. Their method was developed using the NEXTflex Bisulfite-Seq Barcodes, eliminating the need for targeted primer design and thereby eliminating the associated biases.