In a human cell, approximately two meters of DNA are packed within a five-micron nucleus—a spectacular topological challenge solved by the cell through the hierarchical folding of DNA around histone proteins to form nucleosomes, and the compaction of nucleosomes into chromatin (Kornberg, 1974). This hierarchical packaging sequesters inactive genomic regions and leaves biologically active regions – be they promoters, enhancers, or other regulatory elements – accessible to transcription machinery (Gross and Garrard, 1988; Bell et al., 2011). Atop this landscape of physical compaction operates a dynamic epigenetic code that includes DNA methylation, nucleosome positioning, histone composition, and modification, as well as transcription factors, chromatin remodelers, and non-coding RNAs (Kouzarides, 2007; Rinn and Chang, 2012). Cellular phenotypes are substantially governed by epigenetic mechanisms that manipulate the composition, compaction, and nucleoprotein structure of chromatin (Chen and Dent, 2014).
