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Fig. 7 | Genome Medicine

Fig. 7

From: Molecular dissection of germline chromothripsis in a developmental context using patient-derived iPS cells

Fig. 7

Gains and losses of enhancer interactions with the TWIST1 locus in the patient. a 4C-seq data show that TWIST1 mainly contacts a region encompassing three TADs (termed TWIST1 TADs) in the NPCs of the father (cell line UMCU23). The y-axis indicates the number of normalized 4C-seq reads cutoff at 500 normalized reads. TAD boundaries in H1-ESCs were determined by Hi-C analysis by Dixon et al. [38]. ChromHMM analysis of Roadmap ChIP-seq data of primary fibroblasts with high TWIST1 expression indicates that these TWIST1 TADs contain multiple enhancers active in mesodermal cells (shown in purple). The TWIST1 4C-seq data of the patient’s NPCs (UMCU15) shows that TWIST1 has reduced interactions with several of these enhancers (red highlights), which likely had an impact on TWIST1 expression in the patient. b The 4C-seq data, depicted on the derivative chromosome 3 in the patient, shows that TWIST1 gained several ectopic contacts with enhancers active in neural cells in the patient. Enhancer activity was obtained from ChromHMM analysis of Roadmap ChIP-seq data of NPCs derived from differentiation of hESCs. 4C-seq using two of these enhancers as baits confirms the ectopic interactions between the enhancers and TWIST1 (Additional file 1: Figure S8). These ectopic interactions may explain the overexpression of TWIST1 in the patient’s NPCs

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