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Series GSE247056 Query DataSets for GSE247056
Status Public on Apr 02, 2024
Title 3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [RNA-Seq]
Organism Homo sapiens
Experiment type Expression 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 Bulk RNA-seq on cells treated with MYC promoter CRISPRi to assess role of MYC's promoter on enhancer hijacking regulatory network on ecDNA strcutures
 
Contributor(s) Mortenson KL, Zhang X, Varley KE
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Submission date Nov 06, 2023
Last update date Jun 21, 2024
Contact name Xiaoyang Zhang
E-mail(s) xiaoyang.zhang@hci.utah.edu
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)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (4)
GSM7882712 H2170_CRISPRi_NT2_RNA_seq
GSM7882713 H2170_CRISPRi_NT1_RNA_seq
GSM7882714 H2170_CRISPRi_MYCp1_RNA_seq
This SubSeries is part of SuperSeries:
GSE228247 3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression
Relations
BioProject PRJNA1036170

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE247056_RAW.tar 9.1 Mb (http)(custom) TAR (of RESULTS)
SRA Run SelectorHelp
Raw data are available in SRA

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