Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells
| Autor: | Joshua O. Scheys, Pablo Menendez, K. Sue O'Shea, Santiago Morell, Deanna A. Kulpa, Kathleen L. Collins, Jose L. Garcia-Perez, Maria Morell, Christoph C. Carter, John V. Moran, Gary D. Hammer |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Chromatin Immunoprecipitation Embryonal Carcinoma Stem Cells Retroelements Cellular differentiation Genetic Vectors Biology Article Epigenesis Genetic Mice 03 medical and health sciences 0302 clinical medicine Genes Reporter Cell Line Tumor Animals Humans Gene silencing Gene Silencing Gene Zebrafish 030304 developmental biology Regulation of gene expression 0303 health sciences Reporter gene Multidisciplinary Models Genetic Genome Human HIV Cell Differentiation Chromatin 3. Good health Gene Expression Regulation Neoplastic Histone Deacetylase Inhibitors Long Interspersed Nucleotide Elements Cancer research Female Histone deacetylase Moloney murine leukemia virus Genetic Engineering Chromatin immunoprecipitation 030217 neurology & neurosurgery |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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