CapTEs enables locus-specific dissection of transcriptional outputs from reference and nonreference transposable elements
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE205935 | GEO | 2023/08/31
REPOSITORIES: GEO
Similar Datasets
Project description:We introduce a novel method (CELLO-seq) for long-read RNA sequencing at single cell resolution. CELLO-seq allows for full-length RNA sequencing and enables measurement of allelic, isoform and Transposable Element (TE) expression at unique loci. We use CELLO-seq to assess the widespread expression of TEs in 2-cell mouse blastomeres as well as human induced pluripotent stem cells (hiPSCs). Across both species, old and young TEs showed evidence of locus-specific expression, with simulations demonstrating that only a small number of very young elements in the mouse could not be mapped back to with high confidence. Exploring the relationship between the expression of individual elements and putative regulators revealed surprising heterogeneity, with TEs within a class showing different patterns of correlation, suggesting distinct regulatory mechanisms. CELLO-seq thus represents a significant advance in the research of TEs, highlighting that studying TEs in single cells and at single loci resolution is necessary for understanding how such elements are regulated and for gaining insight into their role during development.
2020-10-01 | E-MTAB-9577 | biostudies-arrayexpress
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 lasTEq, 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, lasTEq outperforms current quantitative approaches and is significantly favorable in capturing newly inserted TEs. We also verified that TEs quantified by lasTEq clearly related to euchromatins and heterochromatins in cell line samples. With lasTEq 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 lasTEq, 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, lasTEq outperforms current quantitative approaches and is significantly favorable in capturing newly inserted TEs. We also verified that TEs quantified by lasTEq clearly related to euchromatins and heterochromatins in cell line samples. With lasTEq we anticipate that more accurate quantification can be performed, allowing novel functions of TEs to be uncovered.
2023-09-01 | GSE225377 | GEO
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:Arbuscular mycorrhizal (AM) fungi form mutualistic relationships with most land plant species. AM fungi have long been considered as ancient asexuals. Long-term clonal evolution would be remarkable for a eukaryotic lineage and suggests the importance of alternative mechanisms to promote genetic variability facilitating adaptation. Here, we assessed the potential of transposable elements (TEs) for generating genomic diversity. The dynamic expression of TEs during Rhizophagus irregularis spore development suggests ongoing TE activity. We find Mutator-like elements located near genes belonging to highly expanded gene families. Characterising the epigenomic status of R. irregularis provides evidence of DNA methylation and small RNA production occurring at TE loci. Our results support a potential role for TEs in shaping the genome, and roles for DNA methylation and small RNA-mediated silencing in regulating TEs. A well-controlled balance between TE activity and repression may therefore contribute to genome evolution in AM fungi.
2022-02-17 | PXD025245 | Pride
Project description:Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein-DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of Hi-ChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we show that young TEs display locus- and tissue-specific chromatin profiles in both mice and humans. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome.
2021-08-19 | GSE182305 | GEO
Project description:Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein-DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of Hi-ChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we show that young TEs display locus- and tissue-specific chromatin profiles in both mice and humans. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome.
2021-08-19 | GSE182304 | GEO
Project description:Background: Transposable elements (TEs) represent a substantial fraction of the genomes, playing a major role in evolution, as sources of genetic variability. To fully appraise the role of TE in the acquisition of genetic novelty in genome evolution, we must also consider the impact of their own transcriptional activity. Results: We studied impact of TE transcriptional activity on gene using high-throughput RNA-Seq sequencing in Drosophila melanogaster. TEs, which turn out to be expressed in euchromatin as well as in heterochromatin, interact with genes at different levels. The observed transcription from TEs involve canonical or non-canonical transcription start sites (TSSs) distributed along their sequence. We also find evidences for potential bidirectional transcription from the TE promoter regions where the antisense transcript is co-opted by the host genome as TSSs of a gene. We found that active TEs seem to accumulate in the 5' upstream regions of the genes, and possibly provide an alternative transcript of the nearby gene. Indeed, predominantly, the TE transcript is collinear and overlapping the gene. Apart from the 5' upstream regions, we also found that most active TEs are transcribed on the gene transcript strand. Conversely, few transcripts from TE are anti sense with respect to the gene. This suggests that they have a disruptive action and are counter-selected. The only exceptions are for TEs located into introns, where they could provide another complex way of gene regulation, and in the 3' downstream region, where other mechanisms akin to siRNAs could take place. Finally, we noted several cases where the cryptic TSS is located on TE fragments corresponding to a low complexity sequence. Frequently these TE fragments appear to be over-represented when close to genes, suggesting a possible selected role. Conclusion: Altogether, these results suggest that active transposable elements influence host gene transcription. It is likely that some features of transposable elements have been exaptated in order to enrich the genes repertoire by opening routes to sub- or neo-functionalization. Examination of the transcription produced by transposable elements in D. melanogaster
2014-01-01 | E-GEOD-52472 | biostudies-arrayexpress
Project description:East African cichlid fishes have radiated in an explosive fashion. The (epi)genetic basis for the abundant phenotypic diversity of these fishes remains largely unknown. As transposable elements (TEs) contribute extensively to genome evolution, we reasoned that TEs may have fuelled cichlid radiations. While TE-derived genetic and epigenetic variability has been associated with phenotypic traits, TE expression and epigenetic silencing remain unexplored in cichlids. Here, we profiled TE expression in African cichlids, and describe dynamic expression patterns during embryogenesis and according to sex. Most TE silencing factors are conserved and expressed in cichlids. We describe an expansion of two truncated Piwil1 genes in Lake Malawi/Nyasa cichlids, encoding a Piwi domain with catalytic potential. To further dissect epigenetic silencing of TEs, we focused on small RNA-driven epigenetic silencing. We detect a small RNA population in gonads consistent with an active Piwi-interacting RNA (piRNA) pathway targeting TEs. We uncover fluid genomic origins of piRNAs in closely related cichlid species. This, along with signatures of positive selection in piRNA pathway factors, points towards fast co-evolution of TEs and the piRNA pathway. Our study is the first step to understand the contribution of ongoing TE-host arms races to the cichlid radiations in Africa.
2024-04-02 | PXD047439 | Pride
Project description:Numerous studies over the past decade have elucidated a substantial set of long intergenic noncoding RNAs (lincRNAs). It has since become clear that lincRNAs constitute an important layer of genome regulation across a wide spectrum of species. Yet, the factors governing their evolution and origins remain relatively unexplored. One possible factor that may have shaped lincRNA biology are transposable elements (TEs). Here we set out to comprehensively characterize the TE content of lincRNAs relative to genomic averages and protein coding transcripts. Our analysis of the TE composition across 9241 human lincRNAs revealed that, in sharp contrast to protein coding genes, a striking majority (83%) of lincRNAs contain a TE, and TEs comprise 42% of lincRNA transcript sequences. LincRNA TE composition varies significantly from genomic averages, being depleted of LI and Alu elements and enriched for a broad class of endogenous retroviruses (ERVs). Furthermore, specific TE families occur in biased positions and orientations within lincRNAs, particularly at their transcription start sites, suggesting a role in the origin of those lincRNAs. Finally, we find that TEs can drive gene expression regulation of lincRNAs—we observed a dramatic correlation between lincRNAs containing HERVH elements and almost exclusive expression in pluripotent cells. Conversely, those lincRNAs that are devoid of TEs are more highly expressed in testis. Collectively, TEs pervade lincRNAs and have shaped lincRNA evolution and function via bestowing tissue-specific expression from donated transcriptional regulatory signals. We extracted profiled the transcriptome expression polyadenylated mRNA-Seq. We then used these to reconstruct the transcriptome using de-novo assemblers and identify long non coding RNAs and their expression.
2013-01-22 | E-GEOD-38993 | biostudies-arrayexpress