A number of methods potentially hold promise for uncovering details of chromosome folding at the 2- to 10-nucleosome length scale. We have recently developed a variant of the Hi-C protocol—“Micro-C”—in which micrococcal nuclease is used in place of restriction enzymes to fragment the genome, providing a mononucleosome-resolution chromosome folding assay (Hsieh et al. 2015). Intriguingly, this assay revealed abundant chromosomal interaction domains, similar to the TADs described in mammals and CIDs in Caulobacter crescentis, with strong interactions occurring through the domain but boundaries preventing interactions between adjacent TADs/CIDs. Curiously, CID length in different species is highly divergent when scaled by genomic distance but is relatively conserved when scaled by gene number—TADs in mammals and CIDs in yeast both encompass ∼1–5 genes, with this structure thus occurring over ∼1 Mb scales in mammals but only ∼5 kb in yeast. In terms of 30-nm fiber structure, no periodicity is observed in Micro-C ligation products (e.g., interactions between nucleosome N and nucleosomes N + 6, N + 12, N + 18, etc., as expected from solenoid models), although the use of the short-length
