Cargando…
Mobilization of LINE-1 retrotransposons is restricted by Tex19.1 in mouse embryonic stem cells
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 mobil...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570191/ https://www.ncbi.nlm.nih.gov/pubmed/28806172 http://dx.doi.org/10.7554/eLife.26152 |
_version_ | 1783259135163236352 |
---|---|
author | MacLennan, Marie García-Cañadas, Marta Reichmann, Judith Khazina, Elena Wagner, Gabriele Playfoot, Christopher J Salvador-Palomeque, Carmen Mann, Abigail R Peressini, Paula Sanchez, Laura Dobie, Karen Read, David Hung, Chao-Chun Eskeland, Ragnhild Meehan, Richard R Weichenrieder, Oliver García-Pérez, Jose Luis Adams, Ian R |
author_facet | MacLennan, Marie García-Cañadas, Marta Reichmann, Judith Khazina, Elena Wagner, Gabriele Playfoot, Christopher J Salvador-Palomeque, Carmen Mann, Abigail R Peressini, Paula Sanchez, Laura Dobie, Karen Read, David Hung, Chao-Chun Eskeland, Ragnhild Meehan, Richard R Weichenrieder, Oliver García-Pérez, Jose Luis Adams, Ian R |
author_sort | MacLennan, Marie |
collection | PubMed |
description | 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. DOI: http://dx.doi.org/10.7554/eLife.26152.001 |
format | Online Article Text |
id | pubmed-5570191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-55701912017-08-28 Mobilization of LINE-1 retrotransposons is restricted by Tex19.1 in mouse embryonic stem cells MacLennan, Marie García-Cañadas, Marta Reichmann, Judith Khazina, Elena Wagner, Gabriele Playfoot, Christopher J Salvador-Palomeque, Carmen Mann, Abigail R Peressini, Paula Sanchez, Laura Dobie, Karen Read, David Hung, Chao-Chun Eskeland, Ragnhild Meehan, Richard R Weichenrieder, Oliver García-Pérez, Jose Luis Adams, Ian R eLife Developmental Biology and Stem Cells 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. DOI: http://dx.doi.org/10.7554/eLife.26152.001 eLife Sciences Publications, Ltd 2017-08-14 /pmc/articles/PMC5570191/ /pubmed/28806172 http://dx.doi.org/10.7554/eLife.26152 Text en © 2017, MacLennan et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology and Stem Cells MacLennan, Marie García-Cañadas, Marta Reichmann, Judith Khazina, Elena Wagner, Gabriele Playfoot, Christopher J Salvador-Palomeque, Carmen Mann, Abigail R Peressini, Paula Sanchez, Laura Dobie, Karen Read, David Hung, Chao-Chun Eskeland, Ragnhild Meehan, Richard R Weichenrieder, Oliver García-Pérez, Jose Luis Adams, Ian R Mobilization of LINE-1 retrotransposons is restricted by Tex19.1 in mouse embryonic stem cells |
title | Mobilization of LINE-1 retrotransposons is restricted by
Tex19.1 in mouse embryonic stem cells |
title_full | Mobilization of LINE-1 retrotransposons is restricted by
Tex19.1 in mouse embryonic stem cells |
title_fullStr | Mobilization of LINE-1 retrotransposons is restricted by
Tex19.1 in mouse embryonic stem cells |
title_full_unstemmed | Mobilization of LINE-1 retrotransposons is restricted by
Tex19.1 in mouse embryonic stem cells |
title_short | Mobilization of LINE-1 retrotransposons is restricted by
Tex19.1 in mouse embryonic stem cells |
title_sort | mobilization of line-1 retrotransposons is restricted by
tex19.1 in mouse embryonic stem cells |
topic | Developmental Biology and Stem Cells |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570191/ https://www.ncbi.nlm.nih.gov/pubmed/28806172 http://dx.doi.org/10.7554/eLife.26152 |
work_keys_str_mv | AT maclennanmarie mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT garciacanadasmarta mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT reichmannjudith mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT khazinaelena mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT wagnergabriele mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT playfootchristopherj mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT salvadorpalomequecarmen mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT mannabigailr mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT peressinipaula mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT sanchezlaura mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT dobiekaren mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT readdavid mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT hungchaochun mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT eskelandragnhild mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT meehanrichardr mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT weichenriederoliver mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT garciaperezjoseluis mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells AT adamsianr mobilizationofline1retrotransposonsisrestrictedbytex191inmouseembryonicstemcells |