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An abundant class of non-coding DNA can prevent stochastic gene silencing in the C. elegans germline
Cells benefit from silencing foreign genetic elements but must simultaneously avoid inactivating endogenous genes. Although chromatin modifications and RNAs contribute to maintenance of silenced states, the establishment of silenced regions will inevitably reflect underlying DNA sequence and/or stru...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947018/ https://www.ncbi.nlm.nih.gov/pubmed/27374334 http://dx.doi.org/10.1016/j.cell.2016.05.072 |
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author | Frøkjær-Jensen, Christian Jain, Nimit Hansen, Loren Davis, M Wayne Li, Yongbin Zhao, Di Rebora, Karine Millet, Jonathan RM Liu, Xiao Kim, Stuart K Dupuy, Denis Jorgensen, Erik M Fire, Andrew Z |
author_facet | Frøkjær-Jensen, Christian Jain, Nimit Hansen, Loren Davis, M Wayne Li, Yongbin Zhao, Di Rebora, Karine Millet, Jonathan RM Liu, Xiao Kim, Stuart K Dupuy, Denis Jorgensen, Erik M Fire, Andrew Z |
author_sort | Frøkjær-Jensen, Christian |
collection | PubMed |
description | Cells benefit from silencing foreign genetic elements but must simultaneously avoid inactivating endogenous genes. Although chromatin modifications and RNAs contribute to maintenance of silenced states, the establishment of silenced regions will inevitably reflect underlying DNA sequence and/or structure. Here we demonstrate that a pervasive non-coding DNA feature in Caenorhabditis elegans, characterized by 10-basepair periodic A(n)/T(n)-clusters (PATCs), can license transgenes for germline expression within repressive chromatin domains. Transgenes containing natural or synthetic PATCs are resistant to position effect variegation and stochastic silencing in the germline. Among endogenous genes, intron length and PATC-character undergo dramatic changes as orthologs move from active to repressive chromatin over evolutionary time, indicating a dynamic character to the A(n)/T(n) periodicity. We propose that PATCs form the basis of a cellular immune system, identifying certain endogenous genes in heterochromatic contexts as privileged while foreign DNA can be suppressed with no requirement for a cellular memory of prior exposure. |
format | Online Article Text |
id | pubmed-4947018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-49470182017-07-14 An abundant class of non-coding DNA can prevent stochastic gene silencing in the C. elegans germline Frøkjær-Jensen, Christian Jain, Nimit Hansen, Loren Davis, M Wayne Li, Yongbin Zhao, Di Rebora, Karine Millet, Jonathan RM Liu, Xiao Kim, Stuart K Dupuy, Denis Jorgensen, Erik M Fire, Andrew Z Cell Article Cells benefit from silencing foreign genetic elements but must simultaneously avoid inactivating endogenous genes. Although chromatin modifications and RNAs contribute to maintenance of silenced states, the establishment of silenced regions will inevitably reflect underlying DNA sequence and/or structure. Here we demonstrate that a pervasive non-coding DNA feature in Caenorhabditis elegans, characterized by 10-basepair periodic A(n)/T(n)-clusters (PATCs), can license transgenes for germline expression within repressive chromatin domains. Transgenes containing natural or synthetic PATCs are resistant to position effect variegation and stochastic silencing in the germline. Among endogenous genes, intron length and PATC-character undergo dramatic changes as orthologs move from active to repressive chromatin over evolutionary time, indicating a dynamic character to the A(n)/T(n) periodicity. We propose that PATCs form the basis of a cellular immune system, identifying certain endogenous genes in heterochromatic contexts as privileged while foreign DNA can be suppressed with no requirement for a cellular memory of prior exposure. 2016-06-30 2016-07-14 /pmc/articles/PMC4947018/ /pubmed/27374334 http://dx.doi.org/10.1016/j.cell.2016.05.072 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This manuscript version is made available under the CC BY-NC-ND 4.0 license. |
spellingShingle | Article Frøkjær-Jensen, Christian Jain, Nimit Hansen, Loren Davis, M Wayne Li, Yongbin Zhao, Di Rebora, Karine Millet, Jonathan RM Liu, Xiao Kim, Stuart K Dupuy, Denis Jorgensen, Erik M Fire, Andrew Z An abundant class of non-coding DNA can prevent stochastic gene silencing in the C. elegans germline |
title | An abundant class of non-coding DNA can prevent stochastic gene silencing in the C. elegans germline |
title_full | An abundant class of non-coding DNA can prevent stochastic gene silencing in the C. elegans germline |
title_fullStr | An abundant class of non-coding DNA can prevent stochastic gene silencing in the C. elegans germline |
title_full_unstemmed | An abundant class of non-coding DNA can prevent stochastic gene silencing in the C. elegans germline |
title_short | An abundant class of non-coding DNA can prevent stochastic gene silencing in the C. elegans germline |
title_sort | abundant class of non-coding dna can prevent stochastic gene silencing in the c. elegans germline |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947018/ https://www.ncbi.nlm.nih.gov/pubmed/27374334 http://dx.doi.org/10.1016/j.cell.2016.05.072 |
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