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. 2018 Nov 28;47(3):1239–1254. doi: 10.1093/nar/gky1203

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© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 5. — Differences of low- and high-MNase analysis at local sites. (A) Genome browser snapshot around an accessible enhancer marked by DNase I HS peak (ENCODE, ENCFF567PRQ). (B–E) Averaged MNase-seq profiles around: (B) DNase I HS sites (ENCODE, ENCFF692NCU); average G/C—di-nucleotide content is indicated by the grey line. (C) TSS of highly expressed genes (left panel) and not expressed genes (right panel). FPKM values determined by RNA-Seq analysis (ENCODE, ENCFF000DNW) were used to estimate the level of gene expression. Genes not detected in RNA-Seq analysis (FPKM = 0) were considered as not expressed and those genes showing the 25% highest FPKM values were considered as highly expressed. (D) Active enhancer sites in HeLa cells as defined in (49). (E) CTCF sites (ENCODE, ENCFF002DCW). (F) Heatmaps of high-MNase (left panel) and low-MNase (right panel) are centred on CTCF binding sites and sorted in descending order of ChIP-Seq density at detected CTCF sites. (G) Simulation of low- and high-MNase digestions of a nucleosome array exhibiting nucleosomes with variable MNase sensitivity and hyper-accessible DNA sites. A higher intra-nucleosome cleavage probability p_cut(nuc, AT+) was assigned to a domain, simulating an AT-rich region in the middle of the chromatin strand. In the centre of the nucleosomal array an hyper-accessible site was introduced, representing a fragile nucleosome with markedly increased intra-nucleosome cleavage probability p_cut(nuc, fragile), and the two adjacent DNA linker sites were assigned with enhanced inter-nucleosomal cleavage probability p_cut(linker, hyperaccessible). Chosen cleavage probabilities: p_cut(nuc, AT+) = 2·p_cut(nuc), p_cut(nuc, fragile) = 4·p_cut(nuc), p_cut(linker) = 10·p_cut(nuc), p_cut(linker, hyper-accessible) = 12·p_cut(nuc). (H) Schematic model summarising the results of this study.