There are many broad classes of separation/fractionation methods used to generate DNA populations of interest for epigenomic studies. First, affinity-based methods, such as chromatin immunoprecipitation (ChIP), utilize antibodies specific for proteins or covalently modified peptides to isolate genomic DNA associated with the protein/modification in question. Second, nuclease-susceptibility methods such as MNase-seq, DNase-seq, and ATAC-seq are used to separate regions of the genome based on their susceptibility to enzymatic attack, and typically separate “open” and accessible regions from more compact, often repressed, regions of the genome. Third, chemical susceptibility of DNA and RNA is used in several different epigenomic methods, the most prevalent being the use of bisulfite treatment of DNA or RNA to distinguish between cytosine and 5-methylcytosine, but also including assays based on hydroxyl radical cleavage of the DNA backbone. Fourth, physical separation methods such as sedimentation of isolated chromatin (Gilbert et al. 2004), or partitioning between aqueous and phenol phases (Nagy et al. 2003), have been used to provide insight into packaging of genomic regions. Finally, in addition to separation methods, proximity ligation methods for analysis of chromosomal
