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Series GSE228246 Query DataSets for GSE228246
Status Public on Apr 02, 2024
Title 3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [HiChIP]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Enhancer hijacking, caused by structural alterations, is a common cancer driver event that causes aberrant expression of oncogenes. Unfortunately, enhancer hijacking is difficult to detect due to the complexity of the cancer genome. Here we propose a simple yet robust strategy HAPI (Highly Active Promoter Interactions) to identify and characterize such events by following two rules: 1) oncogenes subject to enhancer hijacking should be potentially highly regulated by enhancers, 2) the hijacked enhancers should contribute an appreciable proportion of an oncogene’s overall enhancer activity. Applying this strategy to HiChIP data we and others generated in 34 cancer cell lines, we identified known enhancer hijacking events and uncovered novel enhancers hijacked by known or potentially novel oncogenes such as CCND1, ETV1, ID4, and NKX2-5, which we validated using CRISPRi assays and RNA-seq analysis. Furthermore, we found that complex enhancer hijacking events connecting genes and enhancers from multiple chromosomal segments are often caused by the formation of extrachromosomal circular DNA (ecDNA). Focusing on ecDNAs harboring the MYC oncogene, one of the most common gene targets of ecDNA, we found that these ecDNAs often stitch additional genes such as CDX2, ERBB2, and NFIB from other chromosomes to the MYC locus. These genes heavily hijack MYC enhancers for their activation, a novel insight into ecDNA biology, suggesting alternative therapeutic targets for MYC ecDNAs. Our study provides an efficient strategy to detect enhancer hijacking events, and more importantly reveals novel mechanisms underlying oncogene activation caused by simple or complex structural alterations.
Overall design H3K27ac HiChIP assays were performed to map enhancer-promoter interactions in cell lines of different cancer types
Contributor(s) Mortenson KL, Zhang X, Varley KE
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Submission date Mar 27, 2023
Last update date Jun 21, 2024
Contact name Xiaoyang Zhang
Organization name University of Utah
Department Oncological Sciences
Lab Zhang
Street address 1950 Circle of Hope Drive
City Salt Lake City
State/province Utah
ZIP/Postal code 84112
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (24)
GSM7117672 MDACAP2B_H3K27ac_HiChIP_rep1
GSM7117673 MDACAP2B_H3K27ac_HiChIP_rep2
GSM7117674 22RV1_H3K27ac_HiChIP
This SubSeries is part of SuperSeries:
GSE228247 3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression
BioProject PRJNA949128

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Supplementary file Size Download File type/resource
GSE228246_RAW.tar 171.8 Mb (http)(custom) TAR (of BEDPE)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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