Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment
Background Interindividual epigenetic variation that occurs systemically must be established prior to gastrulation in the very early embryo and, because it is systemic, can be assessed in easily biopsiable tissues. We employ two independent genome-wide approaches to search for such variants. Results...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | Inglés |
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Springer
2015
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| Online Access: | https://hdl.handle.net/10568/68020 |
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| author | Silver, M.J. Kessler, N.J. Hennig, B.J. Domínguez Salas, Paula Laritsky, E. Baker, M.S. Coarfa, C. Hernández Vargas, H. Castelino, J.M. Routledge, M.N. Yun Yun Gong Herceg, Z. Yong Sun Lee Kwanbok Lee Moore, S.E. Fulford, A.J. Prentice, A.M. Waterland, R.A. |
| author_browse | Baker, M.S. Castelino, J.M. Coarfa, C. Domínguez Salas, Paula Fulford, A.J. Hennig, B.J. Herceg, Z. Hernández Vargas, H. Kessler, N.J. Kwanbok Lee Laritsky, E. Moore, S.E. Prentice, A.M. Routledge, M.N. Silver, M.J. Waterland, R.A. Yong Sun Lee Yun Yun Gong |
| author_facet | Silver, M.J. Kessler, N.J. Hennig, B.J. Domínguez Salas, Paula Laritsky, E. Baker, M.S. Coarfa, C. Hernández Vargas, H. Castelino, J.M. Routledge, M.N. Yun Yun Gong Herceg, Z. Yong Sun Lee Kwanbok Lee Moore, S.E. Fulford, A.J. Prentice, A.M. Waterland, R.A. |
| author_sort | Silver, M.J. |
| collection | Repository of Agricultural Research Outputs (CGSpace) |
| description | Background Interindividual epigenetic variation that occurs systemically must be established prior to gastrulation in the very early embryo and, because it is systemic, can be assessed in easily biopsiable tissues. We employ two independent genome-wide approaches to search for such variants. Results First, we screen for metastable epialleles by performing genomewide bisulfite sequencing in peripheral blood lymphocyte (PBL) and hair follicle DNA from two Caucasian adults. Second, we conduct a genomewide screen for genomic regions at which PBL DNA methylation is affected by season of conception in rural Gambia. Remarkably, both approaches identify the genomically imprinted VTRNA2-1 as a top environmentally responsive epiallele. We demonstrate systemic and stochastic interindividual variation in DNA methylation at the VTRNA2-1 differentially methylated region in healthy Caucasian and Asian adults and show, in rural Gambians, that periconceptional environment affects offspring VTRNA2-1 epigenotype, which is stable over at least 10 years. This unbiased screen also identifies over 100 additional candidate metastable epialleles, and shows that these are associated with cis genomic features including transposable elements. Conclusions The non-coding VTRNA2-1 transcript (also called nc886) is a putative tumor suppressor and modulator of innate immunity. Thus, these data indicating environmentally induced loss of imprinting at VTRNA2-1 constitute a plausible causal pathway linking early embryonic environment, epigenetic alteration, and human disease. More broadly, the list of candidate metastable epialleles provides a resource for future studies of epigenetic variation and human disease. |
| format | Journal Article |
| id | CGSpace68020 |
| institution | CGIAR Consortium |
| language | Inglés |
| publishDate | 2015 |
| publishDateRange | 2015 |
| publishDateSort | 2015 |
| publisher | Springer |
| publisherStr | Springer |
| record_format | dspace |
| spelling | CGSpace680202023-12-08T19:36:04Z Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment Silver, M.J. Kessler, N.J. Hennig, B.J. Domínguez Salas, Paula Laritsky, E. Baker, M.S. Coarfa, C. Hernández Vargas, H. Castelino, J.M. Routledge, M.N. Yun Yun Gong Herceg, Z. Yong Sun Lee Kwanbok Lee Moore, S.E. Fulford, A.J. Prentice, A.M. Waterland, R.A. research health Background Interindividual epigenetic variation that occurs systemically must be established prior to gastrulation in the very early embryo and, because it is systemic, can be assessed in easily biopsiable tissues. We employ two independent genome-wide approaches to search for such variants. Results First, we screen for metastable epialleles by performing genomewide bisulfite sequencing in peripheral blood lymphocyte (PBL) and hair follicle DNA from two Caucasian adults. Second, we conduct a genomewide screen for genomic regions at which PBL DNA methylation is affected by season of conception in rural Gambia. Remarkably, both approaches identify the genomically imprinted VTRNA2-1 as a top environmentally responsive epiallele. We demonstrate systemic and stochastic interindividual variation in DNA methylation at the VTRNA2-1 differentially methylated region in healthy Caucasian and Asian adults and show, in rural Gambians, that periconceptional environment affects offspring VTRNA2-1 epigenotype, which is stable over at least 10 years. This unbiased screen also identifies over 100 additional candidate metastable epialleles, and shows that these are associated with cis genomic features including transposable elements. Conclusions The non-coding VTRNA2-1 transcript (also called nc886) is a putative tumor suppressor and modulator of innate immunity. Thus, these data indicating environmentally induced loss of imprinting at VTRNA2-1 constitute a plausible causal pathway linking early embryonic environment, epigenetic alteration, and human disease. More broadly, the list of candidate metastable epialleles provides a resource for future studies of epigenetic variation and human disease. 2015-12 2015-08-24T20:53:16Z 2015-08-24T20:53:16Z Journal Article https://hdl.handle.net/10568/68020 en Open Access Springer Silver, M.J., Kessler, N.J., Hennig, B.J., Dominguez-Salas, P., Laritsky, E., Baker, M.S., Coarfa, C., Hernandez-Vargas, H., Castelino, J.M., Routledge, M.N., Yun Yun Gong, Herceg, Z., Yong Sun Lee, Kwanbok Lee, Moore, S.E., Fulford, A.J., Prentice, A.M. and Waterland, R.A. 2015. Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment. Genome Biology 16:118 |
| spellingShingle | research health Silver, M.J. Kessler, N.J. Hennig, B.J. Domínguez Salas, Paula Laritsky, E. Baker, M.S. Coarfa, C. Hernández Vargas, H. Castelino, J.M. Routledge, M.N. Yun Yun Gong Herceg, Z. Yong Sun Lee Kwanbok Lee Moore, S.E. Fulford, A.J. Prentice, A.M. Waterland, R.A. Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment |
| title | Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment |
| title_full | Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment |
| title_fullStr | Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment |
| title_full_unstemmed | Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment |
| title_short | Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment |
| title_sort | independent genomewide screens identify the tumor suppressor vtrna2 1 as a human epiallele responsive to periconceptional environment |
| topic | research health |
| url | https://hdl.handle.net/10568/68020 |
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