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. 2018 Nov 26;8:17348. doi: 10.1038/s41598-018-35587-x

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Putative regulatory landscape of the inner ear SE. (a) Right bar plot shows the number of low-methylated regions (LMRs) overlapping known DNase I Hypersensitive Sites (DHS) from the mouse ENCODE project²⁵. The numbers on each bar represent the percent overlap with respect to all LMRs. Left bar plot shows the number of hypersensitive LMRs that overlap CTCF binding sites and H3K4me1 enhancer peaks. The numbers on each bar denote percent overlaps. (b) Examples of experimentally validated mouse non-coding fragments with otic (ear) enhancer activity as assessed in transgenic mice from Vista Enhancer Browser for which we found an overlap with LMRs at one of the three time points. (c) Browser shot of the Gjb2 gene locus, illustrating percent methylation levels, LMRs, unmethylated regions (UMRs) and their putative interactions with target genes. (d) Bar plot showing the number of putative target genes interacting with LMRs and UMRs. The numbers on each bar denote the count of known deafness target genes. (e, f) Heatmap of row normalized -log(P-value) for the relative enrichment across the three time points for transcription factor (TF) motifs present in LMRs (e) UMRs (f) and filtered for expression. Representative TFs are shown on the side.