Triplexator: Detecting nucleic acid triple helices in genomic and transcriptomic data

Buske, Fabian A.; Bauer, Denis C.; Mattick, John S.; Bailey, Timothy L.

doi:10.1101/gr.130237.111

Cited by 191 publications

(186 citation statements)

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“…Pyrimidine stretches within rDNA as potential triplex targeting sites Mouse and human rDNA (BK000964 and U13369.1) were analyzed for potential triplex targeting sites (TTS) using the bioinformatic tool Triplexator (Buske et al 2012). This software integrates the features required for Hoogsteen base-pairing to predict sequences with high potential to form triple helices.…”

Section: Resultsmentioning

confidence: 99%

“…These approaches have revealed that mammalian genomes harbor numerous TTS, which are enriched at gene promoters and regulatory elements (Goñi et al 2004(Goñi et al , 2006Wu et al 2007;Buske et al 2012). In humans and mice, there is on average one specific TTS located ∼100-200 bp upstream of transcription start sites at every 1.3 kb within the genome (Goñi et al 2004;Wu et al 2007;Buske et al 2012).…”

Section: +mentioning

confidence: 99%

“…Predictive approaches for putative triplex targeting sites (TTS), for instance with the bioinformatic software Triplexator (Buske et al 2012), use algorithms based on the assumption that triplex formation follows the canonical binding rules of Hoogsteen base-pairing. These approaches have revealed that mammalian genomes harbor numerous TTS, which are enriched at gene promoters and regulatory elements (Goñi et al 2004(Goñi et al , 2006Wu et al 2007;Buske et al 2012).…”

Section: +mentioning

confidence: 99%

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Purine– and pyrimidine–triple-helix-forming oligonucleotides recognize qualitatively different target sites at the ribosomal DNA locus

Maldonado

Filarsky

Grummt

et al. 2017

RNA

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Triplexes are noncanonical DNA structures, which are functionally associated with regulation of gene expression through ncRNA targeting to chromatin. Based on the rules of Hoogsteen base-pairing, polypurine sequences of a duplex can potentially form triplex structures with single-stranded oligonucleotides. Prediction of triplex-forming sequences by bioinformatics analyses have revealed enrichment of potential triplex targeting sites (TTS) at regulatory elements, mainly in promoters and enhancers, suggesting a potential function of RNA-DNA triplexes in transcriptional regulation. Here, we have quantitatively evaluated the potential of different sequences of human and mouse ribosomal RNA genes (rDNA) to form triplexes at different salt and pH conditions. We show by biochemical and biophysical approaches that some of these predicted sequences form triplexes with high affinity, following the canonical rules for triplex formation. We further show that RNA triplex-forming oligos (TFOs) are more stable than their DNA counterpart, and point mutations strongly affect triplex formation. We further show differential sequence requirements of pyrimidine and purine TFO sequences for efficient binding, depending on the G-C content of the TTS. The unexpected sequence specificity, revealing distinct sequence requirements for purine and pyrimidine TFOs, shows that in addition to the Hoogsteen pairing rules, a sequence code and mutations have to be taken into account to predict genomic TTS.

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Section: Resultsmentioning

confidence: 99%

Section: +mentioning

confidence: 99%

Section: +mentioning

confidence: 99%

See 1 more Smart Citation

Purine– and pyrimidine–triple-helix-forming oligonucleotides recognize qualitatively different target sites at the ribosomal DNA locus

Maldonado

Filarsky

Grummt

et al. 2017

RNA

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“…It is likely that lncRNA are capable of interacting directly with genomic DNA sequence through conventional Watson-Crick base-pairing or through alternative modes such as Hoogsteen base-pairing (Buske et al 2012). As in the aforementioned case of RNA, the abundance of near identical TE elements within genomic DNA offers a plausible model whereby complementary interactions mediated by embedded TE sequences with DNA could target lncRNAs to specific genomic loci (Fig.…”

Section: Type Iib: Dna Bindingmentioning

confidence: 99%

The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs

Johnson

Guigó

2014

RNA

260

231

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Our genome contains tens of thousands of long noncoding RNAs (lncRNAs), many of which are likely to have genetic regulatory functions. It has been proposed that lncRNA are organized into combinations of discrete functional domains, but the nature of these and their identification remain elusive. One class of sequence elements that is enriched in lncRNA is represented by transposable elements (TEs), repetitive mobile genetic sequences that have contributed widely to genome evolution through a process termed exaptation. Here, we link these two concepts by proposing that exonic TEs act as RNA domains that are essential for lncRNA function. We term such elements Repeat Insertion Domains of LncRNAs (RIDLs). A growing number of RIDLs have been experimentally defined, where TE-derived fragments of lncRNA act as RNA-, DNA-, and protein-binding domains. We propose that these reflect a more general phenomenon of exaptation during lncRNA evolution, where inserted TE sequences are repurposed as recognition sites for both protein and nucleic acids. We discuss a series of genomic screens that may be used in the future to systematically discover RIDLs. The RIDL hypothesis has the potential to explain how functional evolution can keep pace with the rapid gene evolution observed in lncRNA. More practically, TE maps may in the future be used to predict lncRNA function.

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“…They found them to be associated with promoters and certain classes of repeat elements (Savage et al, 2013) . Possibilities of searching for non-B DNA (Cer et al, 2011) and specifically triplex/H-DNA exist as well (Buske et al, 2012) (Hon et al, 2013). In this paper, we map the distribution and characteristics of potential triplex-forming sequences (PTS) in human genomic DNA as detected/predicted using the R/Bioconductor package triplex.…”

Section: Introductionmentioning

confidence: 99%

Uneven Distribution of Potential Triplex Sequences in the Human Genome - In Silico Study using the R/Bioconductor Package Triplex

Lexa

Martínek

2014

Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms

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Abstract:Eukaryotic genomes are rich in sequences capable of forming non-B DNA structures. These structures are expected to play important roles in natural regulatory processes at levels above those of individual genes, such as whole genome dynamics or chromatin organization, as well as in processes leading to the loss of these functions, such as cancer development. Recently, a number of authors have mapped the occurrence of potential quadruplex sequences in the human genome and found them to be associated with promoters. In this paper, we set out to map the distribution and characteristics of potential triplex-forming sequences (PTS) in the human genome sequence. Using the R/Bioconductor package triplex, we found these sequences to be excluded from exons, while present mostly in a small number of repetitive sequence classes, especially short sequence tandem repeats (microsatellites), Alu and combined elements, such as SVA. We also introduce a novel way of classifying potential triplex sequences, using a lexicographically minimal rotation of the most frequent k-mer to assign class membership automatically. Members of such classes typically have different propensities to form parallel and antiparallel intramolecular triplexes (H-DNA). We observed an interesting pattern, where the predicted third strands of antiparallel H-DNA were much less likely to contain a deletion than their duplex structural counterpart than were their parallel versions.

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Triplexator: Detecting nucleic acid triple helices in genomic and transcriptomic data

Cited by 191 publications

References 50 publications

Purine– and pyrimidine–triple-helix-forming oligonucleotides recognize qualitatively different target sites at the ribosomal DNA locus

Purine– and pyrimidine–triple-helix-forming oligonucleotides recognize qualitatively different target sites at the ribosomal DNA locus

The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs

Uneven Distribution of Potential Triplex Sequences in the Human Genome - In Silico Study using the R/Bioconductor Package Triplex

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