scholarly journals Tex19.1 Restricts LINE-1 Mobilisation in Mouse Embryonic Stem Cells

2017 ◽  
Author(s):  
Marie MacLennan ◽  
Marta García-Cañadas ◽  
Judith Reichmann ◽  
Elena Khazina ◽  
Carmen Salvador-Palomeque ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Ubiquitin Ligase ◽  
Translational Regulation ◽  
Genome Stability ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Dna Hypomethylation ◽  
Pluripotent Cells ◽  
Genomic Locations

AbstractMobilisation of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution. In humans, retrotransposon mobilisation is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilise in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilisation. We also show that TEX19.1 likely acts, at least in part, through promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover, we show that loss of Tex19.1 increases L1-ORF1p levels and mobilisation of L1 reporters in pluripotent mouse embryonic stem cells implying that Tex19.1 prevents new retrotransposition-mediated mutations from arising in the germline genome. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in the epigenetically dynamic developing mammalian germline.

scholarly journals Mobilization of LINE-1 retrotransposons is restricted by Tex19.1 in mouse embryonic stem cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Marie MacLennan ◽  
Marta García-Cañadas ◽  
Judith Reichmann ◽  
Elena Khazina ◽  
Gabriele Wagner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Translational Regulation ◽  
Genome Stability ◽  
De Novo ◽  
Genetic Disorders ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Dna Hypomethylation ◽  
Genomic Locations

Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization. We also show that TEX19.1 likely acts, at least in part, through promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover, loss of Tex19.1 increases L1-ORF1p levels and L1 mobilization in pluripotent mouse embryonic stem cells, implying that Tex19.1 prevents de novo retrotransposition in the pluripotent phase of the germline cycle. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in mammals.

Mouse embryonic stem cells that survive γ-rays exposure maintain pluripotent differentiation potential and genome stability

2011 ◽  
Vol 227 (3) ◽  
pp. 1242-1249 ◽  
Author(s):  
Paola Rebuzzini ◽  
Diana Pignalosa ◽  
Giuliano Mazzini ◽  
Riccardo Di Liberto ◽  
Antonio Coppola ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Genome Stability ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Differentiation Potential ◽  
Γ Rays

scholarly journals Identification of Novel miRNAs in Mouse Embryonic Stem Cells, Embryonic Fibroblasts, and Reprogrammed Pluripotent Cells

2019 ◽  
Author(s):  
Botao Zhao ◽  
Chunsun Fan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
De Novo ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Mouse Embryonic Stem Cells ◽  
Pluripotent Cells ◽  
Embryonic Fibroblasts ◽  
Species Specific

AbstractMicroRNAs (miRNAs) are a class of non-coding small RNAs that function in almost every known cellular activity. MiRNAs play an important role in gene regulation that controls embryonic stem cell (ESC) pluripotency and differentiation, as well as induced pluripotent stem cell (iPSC) reprogramming. In this study, we identified nine novel miRNAs by mining the deep sequencing dataset from mouse embryonic stem cells, mouse embryonic fibroblasts (MEF) and three kinds of reprogrammed pluripotent cells. Most of them are non-conserved but species-specific and cell-specific miRNAs. Eight miRNAs are derived from gene introns, including a “mirtron” miRNA, miR-novel-41. We also showed that miR-novel-27 is a mouse-specific miRNA and the 5′ arm of its precursor hairpin, embedding the mature miR-novel-27, uniquely exists in mouse species but not in any other Placentalia animals. Notably, the 5′ arm of the pre-miR-novel-27 hairpin shows nearly perfect palindrome to the 3′ arm suggesting that it was generated by inverted duplication of the 3′ arm. By this mechanism, the pre-miR-novel-27 hairpin was de novo gained in the mouse genome. This is a new type of de novo miRNA emergence mechanism in animals, which we called “inverted local half hairpin duplication” here. In addition, very limited nucleotide mutants accumulated on the newly emerged 5′ arm since its birth suggesting an especially young evolutionary history of the miR-novel-27 gene.

scholarly journals Genome-wide and locus-specific DNA hypomethylation in G9a deficient mouse embryonic stem cells

2007 ◽  
Vol 12 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Kohta Ikegami ◽  
Misa Iwatani ◽  
Masako Suzuki ◽  
Makoto Tachibana ◽  
Yoichi Shinkai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Deficient Mouse ◽  
Dna Hypomethylation ◽  
Genome Wide
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