Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression

ABSTRACT: 3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression

PROVIDER: PRJNA949123 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [HiChIP]

Project description: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.

2024-04-02 | GSE228246 | GEO

3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [ChIP-Seq]

2024-04-02 | GSE228166 | GEO

3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [RNA-Seq]

2024-04-02 | GSE247056 | GEO

Structural variants drive context dependent oncogene activation in cancer

Project description:Structural variants drive context dependent oncogene activation in cancer

| PRJNA613064 | ENA

Structural variants drive context dependent oncogene activation in cancer

Project description:Higher order chromatin structure is important for regulation of genes by distal regulatory sequences. Structural variants that alter 3D genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer. However, only a small minority of structural variants are associated with altered gene expression and it remains unclear why certain structural variants lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific rearrangements on oncogene activation. By analyzing Hi-C data from 92 cancer cell lines and patient samples, we identified loci affected by recurrent alterations to 3D genome structure, including oncogenes such as MYC, TERT, and CCND1. Using CRISPR/Cas9 genome engineering to generate de novo structural variants, we show that oncogene activity can be predicted using “Activity-by-Contact” models that consider partner region chromatin contacts and enhancer activity. However, Activity-by-Contact models are only predictive of specific subsets of genes in the genome, suggesting that different classes of genes engage in distinct modes of regulation by distal regulatory elements. These results indicate that structural variants that alter 3D genome organization are widespread in cancer genomes and begin to illustrate predictive rules for the consequences of structural variants on oncogene activation.

2022-10-04 | GSE147123 | GEO

3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression.

Project description:Enhancer hijacking, caused by structural alterations on chromosomes as well as extrachromosomal DNA (ecDNA), is a common cancer driver event. The complexity and ubiquity of structural alterations in cancer genomes make it difficult to identify enhancer hijacking using genome sequencing alone. Here we describe a 3D genomics-based analysis called HAPI (Highly Active Promoter Interactions) to characterize enhancer hijacking caused by structural alterations. HAPI analysis of HiChIP data from 34 cancer cell lines identified novel enhancer hijacking events that involve chromosomal rearrangements and activate both known and potentially novel oncogenes such as MYC, CCND1, ETV1, CRKL, and ID4, which we validated using CRISPRi assays and RNA-seq analysis. Furthermore, we found that ecDNAs often contain multiple oncogenes from different chromosomes, which causes nested enhancer hijacking among them. We found that ecDNAs containing MYC often harbor additional oncogenes from other chromosomes such as CDX2, ERBB2, or CD44 that co-opt MYC's enhancers for their overexpression, which we validated using dual-color DNA FISH and CRISPRi assays. These enhancer hijacking events involving multiple oncogenes on ecDNAs have important implications for therapeutic strategies that either target the co-opting oncogenes or the hijacked enhancers. Our publicly available HAPI analysis tool provides a robust strategy to detect enhancer hijacking and reveals novel insights into oncogene activation caused by chromosomal and extrachromosomal structural alterations.

| S-EPMC10849656 | biostudies-literature

3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [HiChIP]

Project description:3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [HiChIP]

| PRJNA949128 | ENA

3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [RNA-Seq]

Project description:3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [RNA-Seq]

| PRJNA1036170 | ENA

3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [ChIP-Seq]

Project description:3D genomics analysis identifies enhancer hijacking caused by structural alterations and extrachromosomal circular DNA formation [ChIP-Seq]

| PRJNA948422 | ENA

3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-04-01 | GSE228247 | GEO