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| Status |
Public on Sep 25, 2024 |
| Title |
Enhancer activation from transposable elements in extrachromosomal DNA |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Extrachromosomal DNA (ecDNA) is a hallmark of aggressive cancer, contributing to both oncogene amplification and tumor heterogeneity. Here, we used Hi-C, super-resolution imaging, and long-read sequencing to explore the nuclear architecture of MYC-amplified ecDNA in colorectal cancer cells. Intriguingly, we observed frequent spatial proximity between ecDNA and 68 repetitive elements which we called ecDNA-interacting elements or EIEs. To characterize a potential regulatory role of EIEs, we focused on a fragment of the L1M4a1#LINE/L1 which we found to be co-amplified with MYC on ecDNA, gaining enhancer-associated chromatin marks in contrast to its normally silenced state. This EIE, in particular, existed as a naturally occurring structural variant upstream of MYC, gaining oncogenic potential in the transcriptionally permissive ecDNA environment. This EIE sequence is sufficient to enhance MYC expression and is required for cancer cell fitness. These findings suggest that silent repetitive genomic elements can be reactivated on ecDNA, leading to functional cooption and amplification. Repeat element activation on ecDNA represents a mechanism of accelerated evolution and tumor heterogeneity and may have diagnostic and therapeutic potential.
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| Overall design |
To interrogate the conformational state of circular extrachromosomal DNA (ecDNA), we performed Hi-C on COLO 320DM colorectal cancer cells.
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| Contributor(s) |
Kraft K, Murphy SE, Jones MG, Shi Q, Bhargava-Shah A, Luong C, Hung KL, He BH, Li R, Park SK, Weiser NE, Luebeck J, Bafna V, Boeke JD, Mischel PS, Boettiger AN, Chang HY |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Sep 18, 2024 |
| Last update date |
Sep 25, 2024 |
| Contact name |
Matthew G Jones |
| E-mail(s) |
[email protected]
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| Organization name |
Stanford University School of Medicine
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| Street address |
269 Campus Drive
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305-5168 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (2) |
| GSM8523315 |
HiC data for COLO320-DM cell line, Replicate 1. |
| GSM8523316 |
HiC data for COLO320-DM cell line, Replicate 2. |
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| Relations |
| BioProject |
PRJNA1162517 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE277492_RAW.tar |
3.6 Gb |
(http)(custom) |
TAR (of HIC) |
SRA Run Selector |
| Raw data are available in SRA |
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