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Transcriptional regulation of early transposon elements, an active family of mouse long terminal repeat retrotransposons.

ABSTRACT: While early transposon (ETn) endogenous retrovirus (ERV)-like elements are known to be active insertional mutagens in the mouse, little is known about their transcriptional regulation. ETns are transcribed during early mouse embryogenesis in embryonic stem (ES) and embryonic carcinoma (EC) cell lines. Despite their lack of coding potential, some ETns remain transposition competent through their use of reverse transcriptase encoded by a related group of ERVs-MusD elements. In this study, we have confirmed high expression levels of ETn and MusD elements in ES and EC cells and have demonstrated an increase in the copy number of ETnII elements in the EC P19 cell line. Using transient transfections, we have shown that ETnII and MusD LTRs are much more active as promoters in P19 cells than in NIH 3T3 cells, indicating that genomic context and methylation are not the only factors determining endogenous transcriptional activity of ETns. Three sites in the 5' part of the long terminal repeat (LTR) were demonstrated to bind Sp1 and Sp3 transcription factors and were found to be important for high LTR promoter activity in P19 cells, suggesting that as yet unidentified Sp binding partners are involved in the regulation of ETn activity in undifferentiated cells. Finally, we found multiple transcription start sites within the ETn LTR and have shown that the LTR retains significant promoter activity in the absence of its noncanonical TATA box. These findings lend insight into the transcriptional regulation of this family of mobile mouse retrotransposons.

SUBMITTER: Maksakova IA

PROVIDER: S-EPMC1280189 | biostudies-literature | 2005 Nov

REPOSITORIES: biostudies-literature

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Transcriptional regulation of early transposon elements, an active family of mouse long terminal repeat retrotransposons.

Maksakova Irina A IA Mager Dixie L DL

Journal of virology 20051101 22

While early transposon (ETn) endogenous retrovirus (ERV)-like elements are known to be active insertional mutagens in the mouse, little is known about their transcriptional regulation. ETns are transcribed during early mouse embryogenesis in embryonic stem (ES) and embryonic carcinoma (EC) cell lines. Despite their lack of coding potential, some ETns remain transposition competent through their use of reverse transcriptase encoded by a related group of ERVs-MusD elements. In this study, we have ...[more]

PMID: 16254322

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Project description:We identified putative long terminal repeat- (LTR) retrotransposon sequences among the 50,000 random sequence tags (RSTs) obtained by the Génolevures project from genomic libraries of 13 Hemiascomycetes species. In most cases additional sequencing enabled us to assemble the whole sequences of these retrotransposons. These approaches identified 17 distinct families, 10 of which are defined by full-length elements. We also identified five families of solo LTRs that were not associated with retrotransposons. Ty1-like retrotransposons were found in four of five species that are phylogenetically related to Saccharomyces cerevisiae (S. uvarum, S. exiguus, S. servazzii, and S. kluyveri but not Zygosaccharomyces rouxii), and in two of three Kluyveromyces species (K. lactis and K. marxianus but not K. thermotolerans). Only multiply crippled elements could be identified in the K. lactis and S. servazzii strains analyzed, and only solo LTRs could be identified in S. uvarum. Ty4-like elements were only detected in S. uvarum, indicating that these elements appeared recently before speciation of the Saccharomyces sensu stricto species. Ty5-like elements were detected in S. exiguus, Pichia angusta, and Debaryomyces hansenii. A retrotransposon homologous with Tca2 from Candida albicans, an element absent from S. cerevisiae, was detected in the closely related species D. hansenii. A complete Ty3/gypsy element was present in S. exiguus, whereas only partial, often degenerate, sequences resembling this element were found in S. servazzii, Z. rouxii, S. kluyveri, C. tropicalis, and Yarrowica lipolytica. P. farinosa (syn. P. sorbitophila) is currently the only yeast species in which no LTR retrotransposons or remnants have been found. Thorough analysis of protein sequences, structural characteristics of the elements, and phylogenetic relationships deduced from these data allowed us to propose a classification for the Ty1/copia elements of hemiascomycetous yeasts and a model of LTR-retrotransposon evolution in yeasts.

Project description:BackgroundLong terminal repeat retrotransposons are the most abundant transposons in plants. They play important roles in alternative splicing, recombination, gene regulation, and defense mechanisms. Large-scale sequencing projects for plant genomes are currently underway. Software tools are important for annotating long terminal repeat retrotransposons in these newly available genomes. However, the available tools are not very sensitive to known elements and perform inconsistently on different genomes. Some are hard to install or obsolete. They may struggle to process large plant genomes. None can be executed in parallel out of the box and very few have features to support visual review of new elements. To overcome these limitations, we developed LtrDetector, which uses techniques inspired by signal-processing.ResultsWe compared LtrDetector to LTR_Finder and LTRharvest, the two most successful predecessor tools, on six plant genomes. For each organism, we constructed a ground truth data set based on queries from a consensus sequence database. According to this evaluation, LtrDetector was the most sensitive tool, achieving 16-23% improvement in sensitivity over LTRharvest and 21% improvement over LTR_Finder. All three tools had low false positive rates, with LtrDetector achieving 98.2% precision, in between its two competitors. Overall, LtrDetector provides the best compromise between high sensitivity and low false positive rate while requiring moderate time and utilizing memory available on personal computers.ConclusionsLtrDetector uses a novel methodology revolving around k-mer distributions, which allows it to produce high-quality results using relatively lightweight procedures. It is easy to install and use. It is not species specific, performing well using its default parameters on genomes of varying size and repeat content. It is automatically configured for parallel execution and runs efficiently on an ordinary personal computer. It includes a k-mer scores visualization tool to facilitate manual review of the identified elements. These features make LtrDetector an attractive tool for future annotation projects involving long terminal repeat retrotransposons.

Project description:Long terminal repeat (LTR) retrotransposons are highly abundant in plant genomes and require transcriptional activity for their proliferative mode of replication. These sequences exist in plant genomes as diverse sublineages within the main element superfamilies (i.e., gypsy and copia). While transcriptional activity of these elements is increasingly recognized as a regular attribute of plant transcriptomes, it is currently unknown the extent to which different sublineages of these elements are transcriptionally active both within and across species. In the current report, we utilize next generation sequencing methods to examine genomic copy number abundance of diverse LTR retrotransposon sublineages and their corresponding levels of transcriptional activity in three diploid wild sunflower species, Helianthus agrestis, H. carnosus and H. porteri.The diploid sunflower species under investigation differ in genome size 2.75-fold, with 2C values of 22.93 for H. agrestis, 12.31 for H. carnosus and 8.33 for H. porteri. The same diverse gypsy and copia sublineages of LTR retrotransposons were identified across species, but with gypsy sequences consistently more abundant than copia and with global gypsy sequence abundance positively correlated with nuclear genome size. Transcriptional activity was detected for multiple copia and gypsy sequences, with significantly higher activity levels detected for copia versus gypsy. Interestingly, of 11 elements identified as transcriptionally active, 5 exhibited detectable expression in all three species and 3 exhibited detectable expression in two species.Combined analyses of LTR retrotransposon genomic abundance and transcriptional activity across three sunflower species provides novel insights into genome size evolution and transposable element dynamics in this group. Despite considerable variation in nuclear genome size among species, relatively conserved patterns of LTR retrotransposon transcriptional activity were observed, with a highly overlapping set of copia and gypsy sequences observed to be transcriptionally active across species. A higher proportion of copia versus gypsy elements were found to be transcriptionally active and these sequences also were expressed at higher levels.

Dataset Information

Transcriptional regulation of early transposon elements, an active family of mouse long terminal repeat retrotransposons.

Publications

Transcriptional regulation of early transposon elements, an active family of mouse long terminal repeat retrotransposons.

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