TY - JOUR T1 - <em>Tex19.1</em> Restricts LINE-1 Mobilisation in Mouse Embryonic Stem Cells JF - bioRxiv DO - 10.1101/102442 SP - 102442 AU - Marie MacLennan AU - Marta García-Cañadas AU - Judith Reichmann AU - Elena Khazina AU - Carmen Salvador-Palomeque AU - Abigail R. Mann AU - Paula Peressini AU - Laura Sanchez AU - Christopher J. Playfoot AU - David Read AU - Chao-Chun Hung AU - Ragnhild Eskeland AU - Richard R. Meehan AU - Oliver Weichenrieder AU - Jose Luis GarcíaPérez AU - Ian R. Adams Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/02/09/102442.abstract N2 - Mobilisation 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. ER -