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. 2018 Mar 26;9:1226. doi: 10.1038/s41467-018-03538-9

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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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Fig. 3 — Chromatin-state transitions reflect mDA development. a RNA-seq: Volcano plot showing differential gene expression between NPC and mDA neurons. Differentially expressed genes with an adjusted p-value < 0.05 obtained by Wald test are shown. b Volcano plot as in a where differentially expressed and H3K27me3 and/or H3K9me3-marked genes are colored according to: marked in mDA – pink, marked in NPC – green, and marked in both mDA and NPC – gray. c ChIP-seq heatmaps showing the abundance of H3K27me3, H3K4me3, and H3K9me3 as RPKMs ± 10 kb around TSS of genes that were upregulated in mDA and associated with a chromatin state containing H3K27me3 and/or H3K9me3 and d genes that were downregulated in mDA and associated with a chromatin state containing H3K27me3 and/or H3K9me3, respectively. The arrow indicates H3K27me3+ genes that gain H3K9me3 in mDA. e Chromatin-state transitions between NPC and mDA neurons for upregulated genes in mDA. Colored squares indicate transitions that occurred significantly more often than expected (odds ratio, orange = more than expected, blue = less than expected, p < 0.05 according to Fisher’s exact test and adjusted for multiple testing). f Heatmaps of average H3K27me3, H3K4me3, and H3K9me3 RPKMs ± 10 kb around TSS of genes upregulated from NPC to mDA and K4 in NPC and K4 in mDA. g Gene ontology (GO) of the top (−log10 (adj p-value), Fisher’s exact test) biological processes for upregulated genes in mDA that were K4 in NPC and K4 in mDA. h Heatmaps as in f of genes upregulated in mDA and K4/K27 in NPC and K4 in mDA. i GO of the top biological processes for upregulated genes in mDA that were K4/K27 in NPC and K4 in mDA. j Chromatin-state transitions between NPC and mDA neurons for downregulated genes in mDA (e). k Heatmaps as in f of genes downregulated in mDA and K4 in NPC and K4/K27 in mDA. l GO of the top biological processes for downregulated genes in mDA that were K4 in NPC and K4/K27 in mDA. m Heatmaps as in f of genes downregulated in mDA, and categorized as K4/K27 in NPC and K4/K27 in mDA. n GO of the top biological processes for downregulated genes in mDA that were K4/K27 in NPC and K4/K27 in mDA