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Epigenetics is the study of regulatory mechanisms that are not accompanied by the action of genetic elements. Recently, a system-wide extension of epigenetics has been driven by the rapid evolution of genomics technology. This means not simply profiling multiple genes together as gene expression microarrays, but also factoring in the crosstalk among various epigenetic components and extending our focus to relatively uncharted genomic areas, including intergenic and intragenic regions. Although this exciting extension provides many interesting research topics as described in this review, the future expansion of epigenomics to cover multiple samples will offer an even more profound opportunity for systems biology research.