Fig. 3: Transcriptional and epigenetic changes induced by MYCN in ATRX-deficient neuroblastoma cells.
From: MYCN amplification and ATRX mutations are incompatible in neuroblastoma
a Heatmap of the mutations in the O-PDXs and cell lines used in this study. An autopsy sample was also used for molecular profiling. b Micrographs of histologic analysis of the ATRX-mutant neuroblastoma O-PDX and corresponding patient tumor. c Plot of sequence read depth from Illumina sequencing for the ATRX gene in the patient’s germline (blue) and tumor (red), showing somatic deletion of exons 2–11. d Heatmap of the chromHMM states used in this study with functional annotation. e ChromHMM plot of the DIRAS1 gene and a bar plot of the gene’s expression on the right. DNA methylation and H3K27me3 and H3K4me3 ChIP-seq for DIRAS1 for a MYCN-amplified tumor (SJNBL046_X1), an ATRX-mutant tumor (SJNBL047443_X1), and fetal adrenal medulla. f ChIP-seq tracks for a portion of the SLC3A2 gene spanning the promoter in SKNMMMYCN cells in the presence or absence of doxycycline after 4 days in culture. Dashed line indicates the start of transcription. The scales are indicated on the right. g ChromHMM and ChIP-seq for MYCN and RNA PolII for a portion of the SLC3A2 gene spanning the promoter in SKNMMMYCN cells in the presence or absence of doxycycline after 4 days. The dashed lines indicate the region with induction of ChromHMM state 13 that is expanded after MYCN binds the promoter. ChromHMM chromatin Hidden Markov Modeling, FPKM fragments per kilobase of transcript per million mapped reads, O-PDX orthotopic patient-derived xenograft.
