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| Status |
Public on Apr 08, 2021 |
| Title |
Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
|
| Summary |
Extrachromosomal, circular DNA (ecDNA) is emerging as a prevalent yet less characterized oncogenic alteration in cancer genomes. We leverage ChIA-PET and ChIA-Drop chromatin interaction assays to characterize genome-wide ecDNA-mediated chromatin contacts that impact transcriptional programs in cancers. ecDNAs in glioblastoma patient-derived neurosphere and prostate cancer cell cultures are marked by widespread intra-ecDNA and genome-wide chromosomal interactions. ecDNA-chromatin contact foci are characterized by broad and high-level H3K27ac signals converging predominantly on chromosomal genes of increased expression levels. Prostate cancer cells harboring synthetic ecDNA circles composed of characterized enhancers result in the genome-wide activation of chromosomal gene transcription. Deciphering the chromosomal targets of ecDNAs at single-molecule resolution reveals an association with actively expressed oncogenes spatially clustered within ecDNA-directed interaction networks. Our results suggest that ecDNA can function as mobile transcriptional enhancers to promote tumor progression and manifest a potential synthetic aneuploidy mechanism of transcription control in cancer.
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| |
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| Overall design |
Perform the chromatin interaction assay ChIA-PET, ChIA-Drop, H3K27ac ChIPseq and RNAseq to define genome-wide ecDNA-mediated chromatin interactomes and to characterize their functional impact on transcription programs in cancers.
|
| Web link |
https://doi.org/10.1016/j.ccell.2021.03.006
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| |
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| Contributor(s) |
Zhu Y, Tjong H, Wong CH, Gujar A, Wei CL, Verhaak R |
| Citation(s) |
33836152 |
| Submission date |
Jan 07, 2019 |
| Last update date |
Apr 12, 2021 |
| Contact name |
Chia-Lin Wei |
| Organization name |
The Jackson Laboratory
|
| Department |
Genome Technologies
|
| Street address |
10 Discovery Dr
|
| City |
Farmington |
| State/province |
CT |
| ZIP/Postal code |
06032 |
| Country |
USA |
| |
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| Platforms (4)
|
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (49)
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|
| Relations |
| BioProject |
PRJNA513379 |
| SRA |
SRP176485 |
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