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Series GSE180923 Query DataSets for GSE180923
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
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.
 
Overall design RNA-seq of human SW480 colon cancer cells and SW480 knocked-in with PCAT2 gene array (3x) under CMV promoter in replicates.
 
Contributor(s) Ganesan A, Baek S, Sturgill D, Bui M, Dalal Y
Citation(s) 35235361
Submission date Jul 27, 2021
Last update date Mar 10, 2022
Contact name Songjoon Baek
Organization name NCI / NIH
Department CCR
Lab LRBGE
Street address 41 Library Drive
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (4)
GSM5478534 0h rep1, PCAT2 KI
GSM5478535 0h rep2, PCAT2 KI
GSM5478536 0h rep1, Control
This SubSeries is part of SuperSeries:
GSE180959 Oncogenic lncRNAs alter epigenetic memory at a fragile chromosomal site in human cancer cells
Relations
BioProject PRJNA750106
SRA SRP330277

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Supplementary file Size Download File type/resource
GSE180923_RAW.tar 8.6 Mb (http)(custom) TAR (of RESULTS)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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