Altered TE-derived genes leads to pathogenesis of FXD [PacBioRNASeq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE264089 | GEO | 2024/10/30
REPOSITORIES: GEO
Similar Datasets
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
Project description:With an ability to compromise genome integrity, transposable elements (TEs) have significant associations with human diseases. Short-read sequencing has been used to study the expression of TEs; however, the highly repetitive nature of these elements makes multimapping a critical issue. Here we implement LocusMasterTE, an improved quantification method by integrating long-read sequencing. Introducing computed transcript per million(TPM) counts from long-read sequencing as prior distribution during Expectation-Maximization(EM) model in short-read TE quantification, multi-mapped reads are re-assigned to correct expression values. Based on simulated short reads, LocusMasterTE outperforms current quantitative approaches and is significantly favorable in capturing newly inserted TEs. We also verified that TEs quantified by LocusMasterTE clearly related to euchromatins and heterochromatins in cell line samples. With LocusMasterTE we anticipate that more accurate quantification can be performed, allowing novel functions of TEs to be uncovered.
2023-09-01 | GSE225380 | GEO
Project description:With an ability to compromise genome integrity, transposable elements (TEs) have significant associations with human diseases. Short-read sequencing has been used to study the expression of TEs; however, the highly repetitive nature of these elements makes multimapping a critical issue. Here we implement LocusMasterTE, an improved quantification method by integrating long-read sequencing. Introducing computed transcript per million(TPM) counts from long-read sequencing as prior distribution during Expectation-Maximization(EM) model in short-read TE quantification, multi-mapped reads are re-assigned to correct expression values. Based on simulated short reads, LocusMasterTE outperforms current quantitative approaches and is significantly favorable in capturing newly inserted TEs. We also verified that TEs quantified by LocusMasterTE clearly related to euchromatins and heterochromatins in cell line samples. With LocusMasterTE we anticipate that more accurate quantification can be performed, allowing novel functions of TEs to be uncovered.
2023-09-01 | GSE225377 | GEO
Project description:Chromatin accessibility is a hallmark of active regulatory function in the genome and variation of chromatin accessibility across individuals has been shown to contribute to complex traits and disease susceptibility. However, the mechanisms responsible for chromatin variation among different individuals and how this variation contributes to phenotypic diversity remain poorly understood. We examined chromatin accessibility variation in liver tissue from seven strains of adult mice that have phenotypic diversity in response to a high-fat/high-sucrose diet. Remarkably, nearly 40% of the loci with the greatest degree of chromatin variability across the strains are associated with transposable elements (TEs), with evolutionarily younger TEs being particularly enriched for regions of chromatin variation. We found that evolutionary younger and older TEs have differential chromatin accessibility profiles and are enriched for binding sites of different transcription factors, indicating the role of TEs in the evolution of regulatory networks in the liver. We also demonstrate that TE polymorphisms and epigenetic regulation of TEs contribute to regulatory variation across different strains through providing binding sites for liver transcription factors. Intriguingly, variable chromatin loci that are associated with liver metabolism are primarily TE-associated. We demonstrate that TEs contribute to regulatory variation in liver and have downstream effects on metabolism. Our data reveal TEs as a novel and important contributor to regulatory and phenotypic variation in the liver and suggest that regulatory variation at TEs is a major contributor to phenotypic variation in populations. Examination of chromatin accessibility with FAIRE-seq in livers of male mice (A/J, AKR/J, BALB/cJ, C57BL/6J, C3H/HeJ, CBA/J, DBA/2J, BXH2/TyJ, and BXH19/TyJ) fed a high-fat, high-sucrose diet.
2016-07-14 | E-GEOD-75770 | biostudies-arrayexpress
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
Project description:Transposable elements (TEs) are self-mobilizing elements that make up a large fraction of mammalian genomes. PIWI proteins and PIWI interacting RNAs (piRNAs) are a part of a system aimed at controlling and preventing TE proliferation. We examined the TE landscape and piRNA repertoires from three non-model Laurasiatherian mammals (dog, horse and big brown bat) with differing TE complements and proliferation patterns to address questions about the evolutionary relationships between piRNAs and TEs. We found that the genomic abundance of new TEs may not match TE transcription. We speculate that a higher rate of SINE targeting by piRNAs in the horse genome contributed to the reduced SINE insertion rate.
2017-03-26 | GSE56336 | GEO
Project description:Chromatin accessibility is a hallmark of active regulatory function in the genome and variation of chromatin accessibility across individuals has been shown to contribute to complex traits and disease susceptibility. However, the mechanisms responsible for chromatin variation among different individuals and how this variation contributes to phenotypic diversity remain poorly understood. We examined chromatin accessibility variation in liver tissue from seven strains of adult mice that have phenotypic diversity in response to a high-fat/high-sucrose diet. Remarkably, nearly 40% of the loci with the greatest degree of chromatin variability across the strains are associated with transposable elements (TEs), with evolutionarily younger TEs being particularly enriched for regions of chromatin variation. We found that evolutionary younger and older TEs have differential chromatin accessibility profiles and are enriched for binding sites of different transcription factors, indicating the role of TEs in the evolution of regulatory networks in the liver. We also demonstrate that TE polymorphisms and epigenetic regulation of TEs contribute to regulatory variation across different strains through providing binding sites for liver transcription factors. Intriguingly, variable chromatin loci that are associated with liver metabolism are primarily TE-associated. We demonstrate that TEs contribute to regulatory variation in liver and have downstream effects on metabolism. Our data reveal TEs as a novel and important contributor to regulatory and phenotypic variation in the liver and suggest that regulatory variation at TEs is a major contributor to phenotypic variation in populations.
2016-07-14 | GSE75770 | GEO
Project description:DNA is tightly packaged in the human nucleus and is wrapped in complex three-dimensional (3D) structures that have been implicated in regulatory processes However, no comprehensive model describes the formation of the 3D genome. At least 40% of the human genome consists of fossilized inactive transposable element (TE) sequences. A role for TEs in 3D genome structure has been suggested by several studies that illustrate how TEs are involved in 3D genome formation. However mechanisms that mediate the formation of TE-mediated 3D contacts is lacking. As TEs are rich in TF binding sites it seems likely that TFs bound to TEs are responsible for forming the 3D genome structure. We used the comprehensive TF binding data available in human and mouse pluripotent stem cells (PSCs), coupled with HiC data to explore the role of TFs bound to TEs in 3D genome organization. Based on these computational predictions we divide TFs into three main classes, those that utilize TEs to drive 3D genome formation, those that are neutral, and a third class that breaks 3D contacts at specific TEs. We then experimentally validate four proteins, and show that SMARCA5 and MAFK are involved in promoting chromatin contacts at TEs, whilst E2F6 and KDM1A are disruptive.
2024-10-26 | GSE248860 | GEO
Project description:Cancer-specific coding mutations can create neoantigens that can be presented on the cell surface of tumors to trigger immunogenic clearance1–4. However, current cancer vaccine approaches have not been universally effective5; this is especially true in tumors with a low mutational burden which, in turn, carry a low conventional neoantigen load6. Transposable elements (TEs) make up approximately 50% of the human genome and have been discovered to provide cryptic promoters, which can be reactivated with epigenetic manipulations to generate TE-gene chimeric transcripts that can be translated into noncanonical peptides7. Here, we focus on glioblastoma, an aggressive brain cancer with low mutation burden, to explore whether epigenetic therapy can induce TE-chimeric antigens (TEAs) to appreciably increase the antigen repertoire that can be targeted with immunotherapy. We perform comprehensive epigenetic and transcriptomic profiling of three patient-derived glioblastoma stem cell lines (GSCs) and, more importantly, astrocyte and fibroblast primary cell lines that are either proliferating or quiescent, treated with epigenetic therapy drugs to identify treatment-induced TEA (TI-TEA) candidates that are preferentially expressed in cancer cells. Although we verify TI-TEAs are indeed presented on HLA molecules in GSCs thus are promising cancer vaccine candidates, many TEs were also transcriptionally activated in proliferating primary cell lines after epigenetic therapy. This work presents a cautionary but optimistic tale for future efforts in harnessing TI-TEAs for targeted immunotherapy approaches.
2024-06-05 | PXD039893 | Pride
Project description:DNA is tightly packaged in the human nucleus and is wrapped in complex three-dimensional (3D) structures that have been implicated in regulatory processes However, no comprehensive model describes the formation of the 3D genome. At least 40% of the human genome consists of fossilized inactive transposable element (TE) sequences. A role for TEs in 3D genome structure has been suggested by several studies that illustrate how TEs are involved in 3D genome formation. However mechanisms that mediate the formation of TE-mediated 3D contacts is lacking. As TEs are rich in TF binding sites it seems likely that TFs bound to TEs are responsible for forming the 3D genome structure. We used the comprehensive TF binding data available in human and mouse pluripotent stem cells (PSCs), coupled with HiC data to explore the role of TFs bound to TEs in 3D genome organization. Based on these computational predictions we divide TFs into three main classes, those that utilize TEs to drive 3D genome formation, those that are neutral, and a third class that breaks 3D contacts at specific TEs. We then experimentally validate four proteins, and show that SMARCA5 and MAFK are involved in promoting chromatin contacts at TEs, whilst E2F6 and KDM1A are disruptive.
2024-10-26 | GSE248861 | GEO