Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Charting the regulatory landscape of TP53 on transposable elements in cancer [ChIP-seq]

ABSTRACT: The relationship between p53 and transposable elements (TEs) has been obscure. Thus, comprehensive profiling of TE-derived transcripts dynamics under the regulation of p53 provides valuable resources for more clarity in p53’s roles in cancer. In this study, we created three cancer cell lines with p53 genetic status as the only variable and combined long-read RNA-seq and short-read RNA-seq to define TE and TE-derived transcripts’ regulatory dynamics. We identified in total 2,503 transcripts that use TE as potential promoters, among which, 141 to 210 are activated by p53. We found ERVs to be a main driver of potential promoters, followed by LINEs. Epigenomic profiling including chromatin accessibility and DNA methylation provided additional support for active promoter potential for p53 upregulated TE-derived transcripts. Short-term restoration of p53 partially recovered chronic p53-regulated TE-derived transcript profile but gain of function TP53 mutations, R175H and R273H, did not show evidence to act via TE network. Overall, we provide a controlled isogenic cancer cell line system with TP53 mutation status as the only genetic variable, deliver a high confidence TE and TE-derived transcript atlas and comprehensively identify active TE promoters that are direct and indirect targets of p53.

ORGANISM(S): Homo sapiens

PROVIDER: GSE262052 | GEO | 2024/10/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Charting the regulatory landscape of TP53 on transposable elements in cancer [WGBS]

Project description:The relationship between p53 and transposable elements (TEs) has been obscure. Thus, comprehensive profiling of TE-derived transcripts dynamics under the regulation of p53 provides valuable resources for more clarity in p53’s roles in cancer. In this study, we created three cancer cell lines with p53 genetic status as the only variable and combined long-read RNA-seq and short-read RNA-seq to define TE and TE-derived transcripts’ regulatory dynamics. We identified in total 2,503 transcripts that use TE as potential promoters, among which, 141 to 210 are activated by p53. We found ERVs to be a main driver of potential promoters, followed by LINEs. Epigenomic profiling including chromatin accessibility and DNA methylation provided additional support for active promoter potential for p53 upregulated TE-derived transcripts. Short-term restoration of p53 partially recovered chronic p53-regulated TE-derived transcript profile but gain of function TP53 mutations, R175H and R273H, did not show evidence to act via TE network. Overall, we provide a controlled isogenic cancer cell line system with TP53 mutation status as the only genetic variable, deliver a high confidence TE and TE-derived transcript atlas and comprehensively identify active TE promoters that are direct and indirect targets of p53.

2024-10-20 | GSE262054 | GEO

Charting the regulatory landscape of TP53 on transposable elements in cancer [RNA-seq]

2024-10-20 | GSE262053 | GEO

Charting the regulatory landscape of TP53 on transposable elements in cancer [ATAC-seq]

Project description:Comprehensive profiling of transposable element (TE)-derived transcripts dynamics under the regulation of p53 provides valuable resources for more clarity in p53 pleiotropic roles in cancer. In this project, we created three cancer cell lines with p53 genetic status as the only variable and used long-read RNA-seq to profile TE and TE-derived transcripts’ regulatory dynamics. By using both short-read RNA-seq and long-read RNA-seq, novel TE-derived transcripts as a function of p53 status were accurately profiled for the first time. We identified in total 2503 transcripts that use TE as potential promoters, among which, 141 to 210 are activated by p53 across three cancer cell lines. We found ERVs to serve as potential driving promoters, followed by LINEs. Epigenomic information from chromatin accessibility and DNA methylation provided additional support for active promoter potential for p53 upregulated TE-derived transcripts. Short-term restoration of p53 partially recovered chronic p53-regulated TE-derived transcriptional profile; whereas gain of function TP53 mutations, R175H and R273H, did not show evidence to act via TE network. Overall, in this paper, we provide a controlled isogenic cancer cell line system with TP53 mutation status as the only genetic variable, deliver a high confidence TE and TE-derived transcript atlas, and comprehensively identify active TE promoters that are direct and indirect targets of p53.

2024-10-20 | GSE262051 | GEO

Using long-read CAGE sequencing to profile cryptic-promoter derived transcripts and their contribution to the immunopeptidome

Project description:Recent studies have demonstrated that the non-coding genome can produce unannotated proteins as antigens that induce immune response. One major source of this activity is the aberrant epigenetic reactivation of transposable elements (TEs). In tumors, TEs often provide cryptic or alternate promoters, which can generate transcripts that encode tumor-specific unannotated proteins. Thus, TE-derived transcripts have the potential to produce tumor-specific, but recurrent, antigens shared among many tumors. Identification of TE-derived tumor antigens holds the promise to improve cancer immunotherapy approaches; however, current genomics and computational tools are not optimized for their detection. Here we combined CAGE technology with full-length long-read transcriptome sequencing (Long-Read CAGE, or LRCAGE) and developed a suite of computational tools to significantly improve immunopeptidome detection by incorporating TE-derived and other tumor transcripts into the proteome database. By applying our methods to human lung cancer cell line H1299 data, we demonstrated that long-read technology significantly improves mapping of promoters with low mappability scores and LRCAGE guarantees accurate construction of uncharacterized 5’ transcript structure. Unannotated peptides predicted from newly characterized transcripts were readily detectable in whole cell lysate mass-spectrometry data. Incorporating unannotated peptides into the proteome database enabled us to detect non-canonical antigens in HLA-pulldown LC-MS/MS data. At last, we showed that epigenetic treatment increased the number of non-canonical antigens, particularly those encoded by TE-derived transcripts, which might expand the pool of targetable antigens for cancers with low mutational burden.

2023-09-23 | PXD040265 | Pride

Pan-cancer tumor-specific antigens and membrane targets from transposable elements

Project description:Cryptic promoters within transposable elements (TEs) are transcriptionally reactivated in tumors to create novel TE-gene chimeric transcripts, which can produce immunogenic antigens. We performed the most comprehensive screen to date for these TE exaptation events in 33 TCGA tumor types, 675 cancer cell lines, and 11,686 GTEx adult tissue transcriptomes and identified 1,068 TE-exapted candidates with the potential to generate shared tumor-specific TE-chimeric antigens (TS-TEAs). Resultant whole lysate and HLA-pulldown mass spectrometry data confirmed that TS-TEAs are presented on cancer cell surfaces. In addition, we highlight the tumor-specific membrane proteins transcribed from TE promoters that can expose novel epitopes on the extracellular surface of cancer cells. Here, we showcase the high pan-cancer prevalence of TS-TEAs and atypical membrane proteins that can be therapeutically exploited through immunotherapy approaches.

2023-01-21 | PXD033351 | Pride

Altered TE-derived genes leads to pathogenesis of FXD [ShortReadRNASeq]

Project description:We identified known and unknown transposon elements in the cells from healthy donors, FXD patients, and ALL patients by long-read RNA-sequencing. Using these identified TEs, we analyzed the expression of TE-derived genes by shot-read (illumina) RNA-sequencing. We found that expression of some specific TE-derived genes were changed in FXD compared to those in healthy donors. These findings suggested the involvement of modified expressions of TE-derived genes in the pathogenesis of FXD.

2024-10-30 | GSE264090 | GEO

Altered TE-derived genes leads to pathogenesis of FXD [PacBioRNASeq]

2024-10-30 | GSE264089 | GEO

Clinical and Pathologic Response of the Primary Tumor in Women Receiving Neoadjuvant Docetaxel-Capecitabine (+/- Trastuzumab) Chemotherapy

Project description:Results: In subjects who completed treatment and surgery, the pCR and near-complete response rates were 15.8% in HER2-negative and 50% in HER2-positive subjects. When stratified by genomic subtype, subjects of the HER2-enriched subtype had the best response (66.7%), the luminal A (11%) and B (4.8%) subtypes the poorest. Of 147 patients tested for p53 mutations using the AmpliChip test, 78 variants were detected; 55 were missense. The response rate among TP53 mutated patients was 30%, significantly higher than the rate in TP53 wild-type patients (10%, P = .0032). Concordance between AmpliChip mutation status versus IHC staining was 65%, with AmpliChip status being predictive of response and IHC status being not being predictive. Conclusion: Capecitabine plus docetaxel in HER2-negative subjects, and with trastuzumab in HER2-positive subjects, provided a good response rate with fewer cycles. p53 mutational analysis using the AmpliChip p53 assay, and genomic subtyping using the PAM50 assay, were promising predictive tests of response. reference x sample

2011-03-18 | E-GEOD-22358 | biostudies-arrayexpress

Clinical and Pathologic Response of the Primary Tumor in Women Receiving Neoadjuvant Docetaxel-Capecitabine (+/- Trastuzumab) Chemotherapy

2011-03-18 | GSE22358 | GEO

Pan-cancer tumor-specific antigens and membrane targets from transposable elements

Project description:We charted the transcription start sites (TSSs) landscape globally to determine the expressed isoform of each gene and validate the precence of transposable element-derived transcript. Cryptic promoters within transposable elements (TEs) are transcriptionally reactivated in tumors to create novel TE-gene chimeric transcripts, which can produce immunogenic antigens. We performed the most comprehensive screen to date for these TE exaptation events in 33 TCGA tumortypes,675 cancer cell lines, and 11,686 GTEx adult tissue transcriptomes and identified 201,068 TE-exapted candidates with the potential to generate shared tumor-specific TE-chimeric antigens (TS-TEAs). Resultant whole lysate and HLA-pull down mass spectrometry data confirmed that TS-TEAs are presented on cancer cell surfaces. In addition, we highlight the tumor-specific membrane proteins transcribed from TE promoters that can expose novel epitopes on the extracellular surface of cancer cells. Here, we showcase the high pan-cancer prevalence of TS-TEAs and atypical membrane proteins that can be therapeutically exploited through immunotherapy approaches.

2023-01-20 | GSE201021 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data