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GEO help: Mouse over screen elements for information. |
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Status |
Public on Mar 09, 2022 |
Title |
Oncogenic lncRNAs alter epigenetic memory at a fragile chromosomal site in human cancer cells [RNA-seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Chromosome instability is a key event in cancer progression. The essential histone H3 variant CENP-A plays a fundamental role in defining centromere identity, structure, and function, but is innately overexpressed in several types of solid cancers. In the cancer background, excess CENP-A is deposited ectopically on chromosome arms, including at the 8q24/cMYC locus, by invading transcription-coupled H3.3 chaperone pathways. Intriguingly, in many cancers, transcription of lncRNAs is upregulated and correlates with poor prognosis, therapeutic resistance, and cancer recurrence in patients. Here, we report that the transcription of chromosome 8q24-derived oncogenic lncRNAs plays an unanticipated role in altering the chromatin landscape of the 8q24 locus. We report that transcription of oncogenic ncRNAs and associated R-loop formation at the 8q24 genomic locus results in the recruitment of H3.3 chaperone-CENP-A histone variant complexes to 8q24. Finally, we demonstrate that a transgene cassette which encodes a specific oncogenic lncRNA from the 8q24 region integrated into a naïve chromosome locus, recruits CENP-A to the new location specifically in a cis-acting manner. These data provide a plausible mechanistic link between locus-specific oncogenic lncRNAs, aberrant local chromatin structure, and the generation of new epigenetic memory in human cancer cells.
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Overall design |
RNA-seq of human SW480 colon cancer cells and SW480 knocked-in with PCAT2 gene array (3x) under CMV promoter in replicates.
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Contributor(s) |
Ganesan A, Baek S, Sturgill D, Bui M, Dalal Y |
Citation(s) |
35235361 |
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Submission date |
Jul 27, 2021 |
Last update date |
Mar 10, 2022 |
Contact name |
Songjoon Baek |
Organization name |
NCI / NIH
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Department |
CCR
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Lab |
LRBGE
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Street address |
41 Library Drive
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE180959 |
Oncogenic lncRNAs alter epigenetic memory at a fragile chromosomal site in human cancer cells |
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Relations |
BioProject |
PRJNA750106 |
SRA |
SRP330277 |
Supplementary file |
Size |
Download |
File type/resource |
GSE180923_RAW.tar |
8.6 Mb |
(http)(custom) |
TAR (of RESULTS) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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