scholarly journals Genome Stability in Embryonic Stem Cells

Author(s):  
Paola Rebuzzini ◽  
Maurizio Zuccotti ◽  
Carlo Alberto ◽  
Silvia Garag
2011 ◽  
Vol 227 (3) ◽  
pp. 1242-1249 ◽  
Author(s):  
Paola Rebuzzini ◽  
Diana Pignalosa ◽  
Giuliano Mazzini ◽  
Riccardo Di Liberto ◽  
Antonio Coppola ◽  
...  

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Marie MacLennan ◽  
Marta García-Cañadas ◽  
Judith Reichmann ◽  
Elena Khazina ◽  
Gabriele Wagner ◽  
...  

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.


2017 ◽  
Author(s):  
Marie MacLennan ◽  
Marta García-Cañadas ◽  
Judith Reichmann ◽  
Elena Khazina ◽  
Carmen Salvador-Palomeque ◽  
...  

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.


2019 ◽  
Vol 33 (6) ◽  
pp. 6778-6788 ◽  
Author(s):  
Aneta Kohutova ◽  
Jan Raška ◽  
Miriama Kruta ◽  
Monika Seneklova ◽  
Tomas Barta ◽  
...  

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