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Transposable elements in the mammalian embryo: pioneers surviving through stealth and service.

Gerdes P, Richardson SR, Mager DL, Faulkner GJ - Genome Biol. (2016)

Bottom Line: Transposable elements (TEs) are notable drivers of genetic innovation.Over evolutionary time, TE insertions can supply new promoter, enhancer, and insulator elements to protein-coding genes and establish novel, species-specific gene regulatory networks.Here, we discuss recent evidence suggesting that TEs may contribute regulatory innovation to mammalian embryonic and pluripotent states as a means to ward off complete repression by their host genome.

View Article: PubMed Central - PubMed

Affiliation: Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

ABSTRACT
Transposable elements (TEs) are notable drivers of genetic innovation. Over evolutionary time, TE insertions can supply new promoter, enhancer, and insulator elements to protein-coding genes and establish novel, species-specific gene regulatory networks. Conversely, ongoing TE-driven insertional mutagenesis, nonhomologous recombination, and other potentially deleterious processes can cause sporadic disease by disrupting genome integrity or inducing abrupt gene expression changes. Here, we discuss recent evidence suggesting that TEs may contribute regulatory innovation to mammalian embryonic and pluripotent states as a means to ward off complete repression by their host genome.

No MeSH data available.


Long interspersed element-1 (L1) contributes to somatic mosaicism. L1 mobilizes in the brain and early embryo (left) and may, for example: a insert into protein-coding exons; b influence neighboring genes by the spreading of repressive histone modifications, such as methylation (me); c initiate sense or antisense transcription of neighboring genes, thereby creating new transcripts, including open reading frame 0 (ORF0) fusion transcripts, using host gene provided splice acceptor sites, which are translated to fusion proteins; d generate DNA double-strand breaks via the endonuclease activity of L1 ORF2p; and e lead to premature termination of host gene transcripts by providing alternative poly(A) signals
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Fig6: Long interspersed element-1 (L1) contributes to somatic mosaicism. L1 mobilizes in the brain and early embryo (left) and may, for example: a insert into protein-coding exons; b influence neighboring genes by the spreading of repressive histone modifications, such as methylation (me); c initiate sense or antisense transcription of neighboring genes, thereby creating new transcripts, including open reading frame 0 (ORF0) fusion transcripts, using host gene provided splice acceptor sites, which are translated to fusion proteins; d generate DNA double-strand breaks via the endonuclease activity of L1 ORF2p; and e lead to premature termination of host gene transcripts by providing alternative poly(A) signals

Mentions: Although both L1 and ERV retrotransposons are active in the mouse germline [105, 106], their capacity to mobilize during embryogenesis is less clear than for human L1. Quinlan et al., for instance, concluded de novo retrotransposition in mouse iPSCs did not occur, or was very rare [107], in contrast to results for human iPSCs [22, 48, 71]. However, an earlier study found that engineered L1 reporter genes mobilize efficiently in mouse embryos [100]. Interestingly, the vast majority of engineered L1 insertions in these animals were not heritable, perhaps indicating retrotransposition later in embryogenesis [100]. Targeted and whole-genome sequencing applied to mouse pedigrees has, conversely, revealed that endogenous L1 mobilization in early embryogenesis is relatively common and often leads to heritable L1 insertions (SRR and GJF, unpublished data). Polymorphic ERV and nonautonomous SINE insertions are also found in different mouse strains [105, 106]. Although the developmental timing of these events is as yet unresolved, we reason that they can occur in spatiotemporal contexts supporting L1 retrotransposition. It follows that both human and mouse L1s, and probably mouse ERVs, can mobilize in embryonic and pluripotent cells (Fig. 6), as well as gametes. The resultant mosaicism can be deleterious to the host organism or their offspring [101], again reinforcing the need for TE restraint during early development.Fig. 6


Transposable elements in the mammalian embryo: pioneers surviving through stealth and service.

Gerdes P, Richardson SR, Mager DL, Faulkner GJ - Genome Biol. (2016)

Long interspersed element-1 (L1) contributes to somatic mosaicism. L1 mobilizes in the brain and early embryo (left) and may, for example: a insert into protein-coding exons; b influence neighboring genes by the spreading of repressive histone modifications, such as methylation (me); c initiate sense or antisense transcription of neighboring genes, thereby creating new transcripts, including open reading frame 0 (ORF0) fusion transcripts, using host gene provided splice acceptor sites, which are translated to fusion proteins; d generate DNA double-strand breaks via the endonuclease activity of L1 ORF2p; and e lead to premature termination of host gene transcripts by providing alternative poly(A) signals
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4862087&req=5

Fig6: Long interspersed element-1 (L1) contributes to somatic mosaicism. L1 mobilizes in the brain and early embryo (left) and may, for example: a insert into protein-coding exons; b influence neighboring genes by the spreading of repressive histone modifications, such as methylation (me); c initiate sense or antisense transcription of neighboring genes, thereby creating new transcripts, including open reading frame 0 (ORF0) fusion transcripts, using host gene provided splice acceptor sites, which are translated to fusion proteins; d generate DNA double-strand breaks via the endonuclease activity of L1 ORF2p; and e lead to premature termination of host gene transcripts by providing alternative poly(A) signals
Mentions: Although both L1 and ERV retrotransposons are active in the mouse germline [105, 106], their capacity to mobilize during embryogenesis is less clear than for human L1. Quinlan et al., for instance, concluded de novo retrotransposition in mouse iPSCs did not occur, or was very rare [107], in contrast to results for human iPSCs [22, 48, 71]. However, an earlier study found that engineered L1 reporter genes mobilize efficiently in mouse embryos [100]. Interestingly, the vast majority of engineered L1 insertions in these animals were not heritable, perhaps indicating retrotransposition later in embryogenesis [100]. Targeted and whole-genome sequencing applied to mouse pedigrees has, conversely, revealed that endogenous L1 mobilization in early embryogenesis is relatively common and often leads to heritable L1 insertions (SRR and GJF, unpublished data). Polymorphic ERV and nonautonomous SINE insertions are also found in different mouse strains [105, 106]. Although the developmental timing of these events is as yet unresolved, we reason that they can occur in spatiotemporal contexts supporting L1 retrotransposition. It follows that both human and mouse L1s, and probably mouse ERVs, can mobilize in embryonic and pluripotent cells (Fig. 6), as well as gametes. The resultant mosaicism can be deleterious to the host organism or their offspring [101], again reinforcing the need for TE restraint during early development.Fig. 6

Bottom Line: Transposable elements (TEs) are notable drivers of genetic innovation.Over evolutionary time, TE insertions can supply new promoter, enhancer, and insulator elements to protein-coding genes and establish novel, species-specific gene regulatory networks.Here, we discuss recent evidence suggesting that TEs may contribute regulatory innovation to mammalian embryonic and pluripotent states as a means to ward off complete repression by their host genome.

View Article: PubMed Central - PubMed

Affiliation: Mater Research Institute, University of Queensland, TRI Building, Woolloongabba, QLD 4102, Australia.

ABSTRACT
Transposable elements (TEs) are notable drivers of genetic innovation. Over evolutionary time, TE insertions can supply new promoter, enhancer, and insulator elements to protein-coding genes and establish novel, species-specific gene regulatory networks. Conversely, ongoing TE-driven insertional mutagenesis, nonhomologous recombination, and other potentially deleterious processes can cause sporadic disease by disrupting genome integrity or inducing abrupt gene expression changes. Here, we discuss recent evidence suggesting that TEs may contribute regulatory innovation to mammalian embryonic and pluripotent states as a means to ward off complete repression by their host genome.

No MeSH data available.