Exonization of the LTR transposable elements in human genome

Piriyapongsa, Jittima; Polavarapu, Nalini; Borodovsky, Mark; McDonald, John F.

doi:10.1186/1471-2164-8-291

Cited by 53 publications

(40 citation statements)

References 38 publications

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“…similar to those reported for the opossum nPE2 and a consensus CORE-SINE [59% along 70 bp, with a central 45-bp region showing 71% identity (17)], the human ISL1 enhancer and consensus LF-SINE [61% along 55 bp (20)], and the consensus Amn-SINE and human Fgf8 enhancer [70% identity along 170 bp (21)]. Interestingly, a MaLR of the MSTB2 family was recently reported to have been exonized into an alternatively spliced exon of the IL22RA2 gene in primates (34).…”

Section: Discussionmentioning

confidence: 99%

Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

Franchini

López-Leal

Nasif

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

121

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The proopiomelanocortin gene ( POMC ) is expressed in a group of neurons present in the arcuate nucleus of the hypothalamus. Neuron-specific POMC expression in mammals is conveyed by two distal enhancers, named nPE1 and nPE2. Previous transgenic mouse studies showed that nPE1 and nPE2 independently drive reporter gene expression to POMC neurons. Here, we investigated the evolutionary mechanisms that shaped not one but two neuron-specific POMC enhancers and tested whether nPE1 and nPE2 drive identical or complementary spatiotemporal expression patterns. Sequence comparison among representative genomes of most vertebrate classes and mammalian orders showed that nPE1 is a placental novelty. Using in silico paleogenomics we found that nPE1 originated from the exaptation of a mammalian-apparent LTR retrotransposon sometime between the metatherian/eutherian split (147 Mya) and the placental mammal radiation (≈90 Mya). Thus, the evolutionary origin of nPE1 differs, in kind and time, from that previously demonstrated for nPE2, which was exapted from a CORE-short interspersed nucleotide element (SINE) retroposon before the origin of prototherians, 166 Mya. Transgenic mice expressing the fluorescent markers tomato and EGFP driven by nPE1 or nPE2, respectively, demonstrated coexpression of both reporter genes along the entire arcuate nucleus. The onset of reporter gene expression guided by nPE1 and nPE2 was also identical and coincidental with the onset of Pomc expression in the presumptive mouse diencephalon. Thus, the independent exaptation of two unrelated retroposons into functional analogs regulating neuronal POMC expression constitutes an authentic example of convergent molecular evolution of cell-specific enhancers.

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Section: Discussionmentioning

confidence: 99%

Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

Franchini

López-Leal

Nasif

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

121

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“…We analysed the presence of (1) DNAse1 hypersensitive sites, which mark for accessible chromatin; 36 (2) several histone methylation and acetylation marks, which commonly underlie promoter elements; 37 (3) ESTs, which mark for transcription; 38 and (4) DNA repetitive sequences, which have been shown to impact gene regulation. 39,40 We observed that, for all above-mentioned regulatory features, human cadherin introns displayed similar frequencies in comparison to all non-cadherin introns and to the random data set (P40.05, data not shown), with the exception of DNA repetitive sequences. Human cadherin and non-cadherin introns revealed significant differences in terms of frequency of two specific families of repeats: short interspersed nuclear elements (SINE) and long terminal repeats (LTRs).…”

Section: Selection Of Cadherin Superfamily Membersmentioning

confidence: 78%

“…All these repetitive elements are known to be involved in novel regulatory mechanisms and in exonization. 39,40 Given that the occurrence of exonization leads to the creation of new transcriptionally active regions, we analysed cadherin introns in terms of intron position and observed introns in positions 2 and 3 were not only longer but harboured a concomitant increased frequency of MIR, MaLR and CAGE tags in comparison with the rest of the human genome. This clearly suggests that the long cadherin introns at these two positions may in fact encode novel transcribed regulatory elements associated with MIR and MaLR repetitive elements.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the intronic portion of cadherin superfamily members, common cancer orchestrators

et al. 2012

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Cadherins are cell-cell adhesion proteins essential for the maintenance of tissue architecture and integrity, and their impairment is often associated with human cancer. Knowledge regarding regulatory mechanisms associated with cadherin misexpression in cancer is scarce. Specific features of the intronic-structure and intronic-based regulatory mechanisms in the cadherin superfamily are unidentified. This study aims at systematically characterizing the intronic portion of cadherin superfamily members and the identification of intronic regions constituting putative targets/triggers of regulation, using a bioinformatic approach and biological data mining. Our study demonstrates that the cadherin superfamily genes harbour specific characteristics in comparison to all non-cadherin genes, both from the genomic and transcriptional standpoints. Cadherin superfamily genes display higher average total intron number and significantly longer introns than other genes and across the entire vertebrate lineage. Moreover, in the human genome, we observed an uncommon high frequency of MIR (mammalian-wide interspersed repeats) and MaLR (mammalian-wide interspersed repeats, a subtype of LTR) regulatory-associated repetitive elements at 5¢-located introns, concomitantly with increased de novo intronic transcription. Using this approach, we identified cadherin intronic-specific sites that may constitute novel targets/triggers of cadherin superfamily expression regulation. These findings pinpoint the need to identify mechanisms affecting particularly MIR and MaLR elements located in introns 2 and 3 of human cadherin genes, possibly important in the expression modulation of this superfamily in homeostasis and cancer.

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“…We have analyzed more than 100 arbitrarily isolated HERV LTR sequences, including 5Ј, 3Ј, and solitary LTRs, in a transient-transfection assay and found that about one-third of these LTRs are still active and may drive gene expression (2, 36; S. Weinhardt et al, unpublished data). Thus, HERVs and other LTR retrotransposons represent mobile regulatory modules that may contribute to the transcriptional regulation of cellular genes (5,18,28,33,47). There are a number of bona fide examples for the recruitment of HERV LTRs as transcriptional control elements for cellular genes (for a review, see references 16, 23, and 28), among them LTRs belonging to the multicopy families HERV-H (21, 41) and HERV-L (8,10).…”

mentioning

confidence: 99%

Human Endogenous Retroviral Long Terminal Repeat Sequences as Cell Type-Specific Promoters in Retroviral Vectors

Schön

Diem

Leitner

et al. 2009

J Virol

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Exonization of the LTR transposable elements in human genome

Cited by 53 publications

References 38 publications

Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons

Characterization of the intronic portion of cadherin superfamily members, common cancer orchestrators

Human Endogenous Retroviral Long Terminal Repeat Sequences as Cell Type-Specific Promoters in Retroviral Vectors

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