Surveying the epigenomic landscape, one base at a time

Table 1 Strategies for epigenome mapping

Method	Strategy	Features	Base-pair resolution possible?	Reference
MNase digestion	Digests non-occluded DNA	Maps nucleosomes, other DNA-occluding particles	Yes [20, 23]	[11]
DNase I hypersensitivity	Digests non-occluded DNA and nucleosomes with 10 bp periodicity	Maps 'open' chromatin	Yes [30, 44]	[12]
Salt fractionation	Extracts chromatin from intact nuclei with increasing salt concentrations	Maps 'active' and 'nuclear matrix' chromatin	Yes, in combination with MNase digestion	[45]
ChIP	Affinity purification of specific chromatin fragments	Maps protein binding sites	Yes (see ChIP-exo)	[46]
DamID	DNA marking by tethered Dam methyltransferase	In vivo marking of protein-DNA interactions	No	[47]
FAIRE	Differential solubility of 'open' and nucleosomal chromatin by sonication and phenol/chloroform extraction	Maps 'open' chromatin	Maybe	[38]
Sono-seq	Differential solubility of 'open' and nucleosomal chromatin by sonication and phenol/chloroform extraction	Maps 'open' chromatin	Maybe	[39]
CATCH-IT	Metabolic labeling of histones	Measures nucleosome turnover	Maybe	[48]
Genome-wide psoralen crosslinking	Treatment of DNA with the intercalating agent psoralen	Measures helical tension of DNA	No	[49]
ChIP-exo	ChIP followed by exonuclease digestion of immunoprecipitated DNA	Removes non-occluded flanking DNA	Yes	[35]
Targeted chemical cleavage	Targeted chemical cleavage of DNA wrapped around modified nucleosomes	Maps nucleosome positions	Yes	[37]

Methods are listed in chronological order of their first published use in mapping epigenomic features to specific genomic locations. CATCH-IT, covalent attachment of tags to capture histones and identify turnover; ChIP, chromatin immunoprecipitation; ChIP-exo, chromatin immunoprecipitation with exonuclease digestion and high-throughput sequencing; DamID, DNA adenine methyltransferase identification; DNase I, deoxyribonuclease I; FAIRE, formaldehyde-assisted isolation of regulatory elements; MNase, micrococcal nuclease; Sono-seq, sonication of DNA and high-throughput sequencing.

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