Transposable elements become active and mobile in the genomes of aging mammalian somatic tissues.
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ABSTRACT:
SUBMITTER: De Cecco M
PROVIDER: S-EPMC3883704 | biostudies-literature | 2013 Dec
REPOSITORIES: biostudies-literature
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Project description:BackgroundDespite the long-held assumption that transposons are normally only expressed in the germ-line, recent evidence shows that transcripts of transposable element (TE) sequences are frequently found in the somatic cells. However, the extent of variation in TE transcript levels across different tissues and different individuals are unknown, and the co-expression between TEs and host gene mRNAs have not been examined.ResultsHere we report the variation in TE derived transcript levels across tissues and between individuals observed in the non-tumorous tissues collected for The Cancer Genome Atlas. We found core TE co-expression modules consisting mainly of transposons, showing correlated expression across broad classes of TEs. Despite this co-expression within tissues, there are individual TE loci that exhibit tissue-specific expression patterns, when compared across tissues. The core TE modules were negatively correlated with other gene modules that consisted of immune response genes in interferon signaling. KRAB Zinc Finger Proteins (KZFPs) were over-represented gene members of the TE modules, showing positive correlation across multiple tissues. But we did not find overlap between TE-KZFP pairs that are co-expressed and TE-KZFP pairs that are bound in published ChIP-seq studies.ConclusionsWe find unexpected variation in TE derived transcripts, within and across non-tumorous tissues. We describe a broad view of the RNA state for non-tumorous tissues exhibiting higher level of TE transcripts. Tissues with higher level of TE transcripts have a broad range of TEs co-expressed, with high expression of a large number of KZFPs, and lower RNA levels of immune genes.
| S-EPMC6720085 | biostudies-literature
Project description:BackgroundThe Tc1/mariner superfamily of transposable elements (TEs) is widespread in animal genomes. Mariner-like elements, which bear a DDD triad catalytic motif, have been identified in a wide range of flowering plant species. However, as the founding member of the superfamily, Tc1-like elements that bear a DD34E triad catalytic motif are only known to unikonts (animals, fungi, and Entamoeba).ResultsHere we report the identification of Tc1-like elements (TLEs) in plant genomes. These elements bear the four terminal nucleotides and the characteristic DD34E triad motif of Tc1 element. The two TLE families (PpTc1, PpTc2) identified in the moss (Physcomitrella patens) genome contain highly similar copies. Multiple copies of PpTc1 are actively transcribed and the transcripts encode intact full length transposase coding sequences. TLEs are also found in angiosperm genome sequence databases of rice (Oryza sativa), dwarf birch (Betula nana), cabbage (Brassica rapa), hemp (Cannabis sativa), barley (Hordium valgare), lettuce (Lactuta sativa), poplar (Populus trichocarpa), pear (Pyrus x bretschneideri), and wheat (Triticum urartu).ConclusionsThis study extends the occurrence of TLEs to the plant phylum. The elements in the moss genome have amplified recently and may still be capable of transposition. The TLEs are also present in angiosperm genomes, but apparently much less abundant than in moss.
| S-EPMC4054914 | biostudies-literature
Project description:Chromatin looping is important for gene regulation, and studies of 3D chromatin structure across species and cell types have improved our understanding of the principles governing chromatin looping. However, 3D genome evolution and its relationship with natural selection remains largely unexplored. In mammals, the CTCF protein defines the boundaries of most chromatin loops, and variations in CTCF occupancy are associated with looping divergence. While many CTCF binding sites fall within transposable elements (TEs), their contribution to 3D chromatin structural evolution is unknown. Here we report the relative contributions of TE-driven CTCF binding site expansions to conserved and divergent chromatin looping in human and mouse. We demonstrate that TE-derived CTCF binding divergence may explain a large fraction of variable loops. These variable loops contribute significantly to corresponding gene expression variability across cells and species, possibly by refining sub-TAD-scale loop contacts responsible for cell-type-specific enhancer-promoter interactions.
| S-EPMC7156512 | biostudies-literature
Project description:Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF, which shapes the 3D genome by creating loops, domains, compartment borders and RNA-DNA interactions, all of which play a role in the compact packaging of DNA and have the potential to facilitate regulatory function. In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using several 3D genome mapping technologies. We show that specific (sub-)families of TEs have contributed to lineage-specific 3D chromatin structures across mammalian species. In many cases, these loops may facilitate interaction between distant cis-regulatory elements and target genes, and domains may segregate chromatin state to impact gene expression in a lineage-specific manner. An experimental validation of our analytical findings using CRISPR-Cas9 to delete a candidate TE resulted in disruption of species-specific 3D chromatin structure. Taken together, we comprehensively quantify and selectively validate our finding that TEs contribute to 3D genome organization and may, in some cases, impact gene regulation during the course of mammalian evolution.
2023-01-16 | GSE222526 | GEO
Project description:Transposable elements (TEs) are genomic sequences that can move, multiply, and often form sizable fractions of vertebrate genomes. Fish belong to a unique group of vertebrates, since their karyotypes and genome sizes are more diverse and complex, with probably higher diversity and evolution specificity of TE. To investigate the characteristics of fish TEs, we compared the mobilomes of 39 species, and observed significant variation of TE content in fish (from 5% in pufferfish to 56% in zebrafish), along with a positive correlation between fish genome size and TE content. In different classification hierarchies, retrotransposons (class), long terminal repeat (order), as well as Helitron, Maverick, Kolobok, CMC, DIRS, P, I, L1, L2, and 5S (superfamily) were all positively correlated with fish genome size. Consistent with previous studies, our data suggested fish genomes to not always be dominated by DNA transposons; long interspersed nuclear elements are also prominent in many species. This study suggests CR1 distribution in fish genomes to be obviously regular, and provides new clues concerning important events in vertebrate evolution. Altogether, our results highlight the importance of TEs in the structure and evolution of fish genomes and suggest fish species diversity to parallel transposon content diversification.
| S-EPMC6817897 | biostudies-other
Project description:Transposable elements (TEs) are selfish genetic elements that mobilize in genomes via transposition or retrotransposition and often make up large fractions of vertebrate genomes. Here, we review the current understanding of vertebrate TE diversity and evolution in the context of recent advances in genome sequencing and assembly techniques. TEs make up 4-60% of assembled vertebrate genomes, and deeply branching lineages such as ray-finned fishes and amphibians generally exhibit a higher TE diversity than the more recent radiations of birds and mammals. Furthermore, the list of taxa with exceptional TE landscapes is growing. We emphasize that the current bottleneck in genome analyses lies in the proper annotation of TEs and provide examples where superficial analyses led to misleading conclusions about genome evolution. Finally, recent advances in long-read sequencing will soon permit access to TE-rich genomic regions that previously resisted assembly including the gigantic, TE-rich genomes of salamanders and lungfishes.
| S-EPMC5381603 | biostudies-literature
Project description:Transposable elements comprise a large proportion of animal genomes. Transposons can have detrimental effects on genome stability but also offer positive roles for genome evolution and gene expression regulation. Proper balance of the positive and deleterious effects of transposons is crucial for cell homeostasis and requires a mechanism that tightly regulates their expression. Herein we describe the expression of DNA transposons of the Tc1/mariner superfamily during Xenopus development. Sense and antisense transcripts containing complete Tc1-2_Xt were detected in Xenopus embryos. Both transcripts were found in zygotic stages and were mainly localized in Spemann's organizer and neural tissues. In addition, the Tc1-like elements Eagle, Froggy, Jumpy, Maya, Xeminos and TXr were also expressed in zygotic stages but not oocytes in X. tropicalis. Interestingly, although Tc1-2_Xt transcripts were not detected in Xenopus laevis embryos, transcripts from other two Tc1-like elements (TXr and TXz) presented a similar temporal and spatial pattern during X. laevis development. Deep sequencing analysis of Xenopus tropicalis gastrulae showed that PIWI-interacting RNAs (piRNAs) are specifically derived from several Tc1-like elements. The localized expression of Tc1-like elements in neural tissues suggests that they could play a role during the development of the Xenopus nervous system.
| S-EPMC3144230 | biostudies-literature
Project description:BackgroundDetection of newly transposed events by transposable elements (TEs) from next generation sequence (NGS) data is difficult, due to their multiple distribution sites over the genome containing older TEs. The previously reported Transposon Insertion Finder (TIF) detects TE transpositions on the reference genome from NGS short reads using end sequences of target TE. TIF requires the sequence of target TE and is not able to detect transpositions for TEs with an unknown sequence.ResultThe new algorithm Transposable Element Finder (TEF) enables the detection of TE transpositions, even for TEs with an unknown sequence. TEF is a finding tool of transposed TEs, in contrast to TIF as a detection tool of transposed sites for TEs with a known sequence. The transposition event is often accompanied with a target site duplication (TSD). Focusing on TSD, two algorithms to detect both ends of TE, TSDs and target sites are reported here. One is based on the grouping with TSDs and direct comparison of k-mers from NGS without similarity search. The other is based on the junction mapping of TE end sequence candidates. Both methods succeed to detect both ends and TSDs of known active TEs in several tests with rice, Arabidopsis and Drosophila data and discover several new TEs in new locations. PCR confirmed the detected transpositions of TEs in several test cases in rice.ConclusionsTEF detects transposed TEs with TSDs as a result of TE transposition, sequences of both ends and their inserted positions of transposed TEs by direct comparison of NGS data between two samples. Genotypes of transpositions are verified by counting of junctions of head and tail, and non-insertion sequences in NGS reads. TEF is easy to run and independent of any TE library, which makes it useful to detect insertions from unknown TEs bypassed by common TE annotation pipelines.
| S-EPMC9682801 | biostudies-literature
Project description:Comprising nearly half of the human and mouse genomes, transposable elements (TEs) are found within most genes. Although the vast majority of TEs in introns are fixed in the species and presumably exert no significant effects on the enclosing gene, some markedly perturb transcription and result in disease or a mutated phenotype. Factors determining the likelihood that an intronic TE will affect transcription are not clear. In this study, we examined intronic TE distributions in both human and mouse and found several factors that likely contribute to whether a particular TE can influence gene transcription. Specifically, we observed that TEs near exons are greatly underrepresented compared to random distributions, but the size of these "underrepresentation zones" differs between TE classes. Compared to elsewhere in introns, TEs within these zones are shorter on average and show stronger orientation biases. Moreover, TEs in extremely close proximity (<20 bp) to exons show a strong bias to be near splice-donor sites. Interestingly, disease-causing intronic TE insertions show the opposite distributional trends, and by examining expressed sequence tag (EST) databases, we found that the proportion of TEs contributing to chimeric TE-gene transcripts is significantly higher within their underrepresentation zones. In addition, an analysis of predicted splice sites within human long terminal repeat (LTR) elements showed a significantly lower total number and weaker strength for intronic LTRs near exons. Based on these factors, we selectively examined a list of polymorphic mouse LTR elements in introns and showed clear evidence of transcriptional disruption by LTR element insertions in the Trpc6 and Kcnh6 genes. Taken together, these studies lend insight into the potential selective forces that have shaped intronic TE distributions and enable identification of TEs most likely to exert transcriptional effects on genes.
| S-EPMC3088655 | biostudies-literature
Project description:Background Transposable elements (TE) comprise nearly half of the human genome and their insertions have profound effects to human genetic diversification and as well as disease. Despite their abovementioned significance, there is no consensus on the TE subfamilies that remain active in the human genome. In this study, we therefore developed a novel statistical test for recently mobile subfamilies (RMSs), based on patterns of overlap with > 100,000 polymorphic indels. Results Our analysis produced a catalogue of 20 high-confidence RMSs, which excludes many false positives in public databases. Intriguingly though, it includes HERV-K, an LTR subfamily previously thought to be extinct. The RMS catalogue is strongly enriched for contributions to germline genetic disorders (P = 1.1e-10), and thus constitutes a valuable resource for diagnosing disorders of unknown aetiology using targeted TE-insertion screens. Remarkably, RMSs are also highly enriched for somatic insertions in diverse cancers (P = 2.8e-17), thus indicating strong correlations between germline and somatic TE mobility. Using CRISPR/Cas9 deletion, we show that an RMS-derived polymorphic TE insertion increased the expression of RPL17, a gene associated with lower survival in liver cancer. More broadly, polymorphic TE insertions from RMSs were enriched near genes with allele-specific expression, suggesting widespread effects on gene regulation. Conclusions By using a novel statistical test we have defined a catalogue of 20 recently mobile transposable element subfamilies. We illustrate the gene regulatory potential of RMS-derived polymorphic TE insertions, using CRISPR/Cas9 deletion in vitro on a specific candidate, as well as by genome wide analysis of allele-specific expression. Our study presents novel insights into TE mobility and regulatory potential and provides a key resource for human disease genetics and population history studies. Supplementary Information The online version contains supplementary material available at 10.1186/s12864-021-08085-0.
| S-EPMC8567694 | biostudies-literature