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Fig. 5. Transcription and epigenetic landscape in the different origin classes. a Venn diagrams showing the origin distribution between transcribed and intergenic regions in Control and PhenDC3-treated mES cells, and random distribution (Genome). Replication initiation sites are enriched in gene regions. b Genomic localization of the different classes of origins relative to transcription. Downregulated origins (suppressed and reduced) are mainly located at promoters. Random origins (dotted lines) are equally distributed in transcription-related regions. c Epigenetic marks associated with the different origin classes. All tested open chromatin marks were enriched around reduced and suppressed origins. New and reinforced origins were located mainly in highly methylated regions. d GSEA analysis of origins situated at promoters (TSS ± 2 kb, left panels) or in transcribed regions (TSS + 10 kb, right panels) for each class. A plot is drawn for each gene set. The x-axis of each plot represents differentially expressed genes ranked from upregulated (on the left) to downregulated (on the right). The enrichment score is indicated on the y-axis. The black horizontal bar indicates the genes present in the gene set. The highest enrichment score indicates the enrichment. If this score is on the left, the enrichment is higher for upregulated genes; if it is on the right, the enrichment is higher for the downregulated genes. Origins associated with the TSS follow the transcription changes upon G4 stabilization, whereas origins located in transcribed regions are insensitive to changes in transcription levels. At gene promoters, GSEA results show a significant association of downregulated genes with the suppressed origin class (after multi-testing correction using the Benjamini–Hochberg method, adjusted p < 0.03). The other origin classes show a similar trend, without reaching significance Image published in: Prorok P et al. (2019) © The Author(s) 2019. This image is reproduced with permission of the journal and the copyright holder. This is an open-access article distributed under the terms of the Creative Commons Attribution license Larger Image Printer Friendly View |