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Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells

Long INterspersed Element-1 (LINE-1 or L1) retrotransposition continues to impact human genome evolution1,2. L1s can retrotranspose in the germline, during early development, and in select somatic cells3,4,5,6,7,8; however, the host response to L1 retrotransposition remains largely unexplored. Here,...

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Autores principales: Garcia-Perez, Jose L., Morell, Maria, Scheys, Joshua O., Kulpa, Deanna A., Morell, Santiago, Carter, Christoph C., Hammer, Gary D., Collins, Kathleen L., O’Shea, K. Sue, Menendez, Pablo, Moran, John V.
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034402/
https://www.ncbi.nlm.nih.gov/pubmed/20686575
http://dx.doi.org/10.1038/nature09209
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author Garcia-Perez, Jose L.
Morell, Maria
Scheys, Joshua O.
Kulpa, Deanna A.
Morell, Santiago
Carter, Christoph C.
Hammer, Gary D.
Collins, Kathleen L.
O’Shea, K. Sue
Menendez, Pablo
Moran, John V.
author_facet Garcia-Perez, Jose L.
Morell, Maria
Scheys, Joshua O.
Kulpa, Deanna A.
Morell, Santiago
Carter, Christoph C.
Hammer, Gary D.
Collins, Kathleen L.
O’Shea, K. Sue
Menendez, Pablo
Moran, John V.
author_sort Garcia-Perez, Jose L.
collection PubMed
description Long INterspersed Element-1 (LINE-1 or L1) retrotransposition continues to impact human genome evolution1,2. L1s can retrotranspose in the germline, during early development, and in select somatic cells3,4,5,6,7,8; however, the host response to L1 retrotransposition remains largely unexplored. Here, we show that reporter genes introduced into the genome of various human embryonic carcinoma-derived cell lines (ECs) by L1 retrotransposition are rapidly and efficiently silenced either during or immediately after their integration. Treating ECs with histone deacetylase inhibitors (IHDACs) rapidly reverses this silencing, and chromatin immunoprecipitation (ChIP) experiments revealed that reactivation of the reporter gene was correlated with changes in chromatin status at the L1 integration site. Under our assay conditions, rapid silencing also was observed when reporter genes were delivered into ECs by mouse L1s and a zebrafish LINE-2 element, but not when similar reporter genes were delivered into ECs by Moloney murine leukemia virus (MMLV) or human immunodeficiency virus (HIV), suggesting these integration events are silenced by distinct mechanisms. Finally, we demonstrate that subjecting ECs to culture conditions that promote differentiation attenuates the silencing of reporter genes delivered by L1 retrotransposition, but that differentiation, per se, is not sufficient to reactivate previously silenced reporter genes. Thus, our data suggest that ECs differ from many differentiated cells in their ability to silence reporter genes delivered by L1 retrotransposition.
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spelling pubmed-30344022011-02-07 Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells Garcia-Perez, Jose L. Morell, Maria Scheys, Joshua O. Kulpa, Deanna A. Morell, Santiago Carter, Christoph C. Hammer, Gary D. Collins, Kathleen L. O’Shea, K. Sue Menendez, Pablo Moran, John V. Nature Article Long INterspersed Element-1 (LINE-1 or L1) retrotransposition continues to impact human genome evolution1,2. L1s can retrotranspose in the germline, during early development, and in select somatic cells3,4,5,6,7,8; however, the host response to L1 retrotransposition remains largely unexplored. Here, we show that reporter genes introduced into the genome of various human embryonic carcinoma-derived cell lines (ECs) by L1 retrotransposition are rapidly and efficiently silenced either during or immediately after their integration. Treating ECs with histone deacetylase inhibitors (IHDACs) rapidly reverses this silencing, and chromatin immunoprecipitation (ChIP) experiments revealed that reactivation of the reporter gene was correlated with changes in chromatin status at the L1 integration site. Under our assay conditions, rapid silencing also was observed when reporter genes were delivered into ECs by mouse L1s and a zebrafish LINE-2 element, but not when similar reporter genes were delivered into ECs by Moloney murine leukemia virus (MMLV) or human immunodeficiency virus (HIV), suggesting these integration events are silenced by distinct mechanisms. Finally, we demonstrate that subjecting ECs to culture conditions that promote differentiation attenuates the silencing of reporter genes delivered by L1 retrotransposition, but that differentiation, per se, is not sufficient to reactivate previously silenced reporter genes. Thus, our data suggest that ECs differ from many differentiated cells in their ability to silence reporter genes delivered by L1 retrotransposition. 2010-08-05 /pmc/articles/PMC3034402/ /pubmed/20686575 http://dx.doi.org/10.1038/nature09209 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Garcia-Perez, Jose L.
Morell, Maria
Scheys, Joshua O.
Kulpa, Deanna A.
Morell, Santiago
Carter, Christoph C.
Hammer, Gary D.
Collins, Kathleen L.
O’Shea, K. Sue
Menendez, Pablo
Moran, John V.
Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells
title Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells
title_full Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells
title_fullStr Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells
title_full_unstemmed Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells
title_short Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells
title_sort epigenetic silencing of engineered l1 retrotransposition events in human embryonic carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034402/
https://www.ncbi.nlm.nih.gov/pubmed/20686575
http://dx.doi.org/10.1038/nature09209
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