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Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells
Transposable elements (TEs) compose about 40% of the murine genome. Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic diversification and genome stability. Therefore, transcription and transposition activities of retrotransposons are tightly controlled. Here, we show...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716208/ https://www.ncbi.nlm.nih.gov/pubmed/29036642 http://dx.doi.org/10.1093/nar/gkx841 |
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author | Dai, Qian Shen, Yang Wang, Yan Wang, Xin Francisco, Joel Celio Luo, Zhuojuan Lin, Chengqi |
author_facet | Dai, Qian Shen, Yang Wang, Yan Wang, Xin Francisco, Joel Celio Luo, Zhuojuan Lin, Chengqi |
author_sort | Dai, Qian |
collection | PubMed |
description | Transposable elements (TEs) compose about 40% of the murine genome. Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic diversification and genome stability. Therefore, transcription and transposition activities of retrotransposons are tightly controlled. Here, we show that the Krüppel-like zinc finger protein Zfp281 directly binds and suppresses a subset of retrotransposons, including the active young L1 repeat elements, in mouse embryonic stem (ES) cells. In addition, we find that Zfp281-regulated L1s are highly enriched for 5-hydroxymethylcytosine (5hmC) and H3K4me3. The COMPASS-like H3K4 methyltransferase Mll2 is the major H3K4me3 methylase at the Zfp281-regulated L1s and required for their proper expression. Our studies also reveal that Zfp281 functions partially through recruiting the L1 regulators DNA hydroxymethylase Tet1 and Sin3A, and restricting Mll2 at these active L1s, leading to their balanced expression. In summary, our data indicate an instrumental role of Zfp281 in suppressing the young active L1s in mouse ES cells. |
format | Online Article Text |
id | pubmed-5716208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57162082017-12-08 Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells Dai, Qian Shen, Yang Wang, Yan Wang, Xin Francisco, Joel Celio Luo, Zhuojuan Lin, Chengqi Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Transposable elements (TEs) compose about 40% of the murine genome. Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic diversification and genome stability. Therefore, transcription and transposition activities of retrotransposons are tightly controlled. Here, we show that the Krüppel-like zinc finger protein Zfp281 directly binds and suppresses a subset of retrotransposons, including the active young L1 repeat elements, in mouse embryonic stem (ES) cells. In addition, we find that Zfp281-regulated L1s are highly enriched for 5-hydroxymethylcytosine (5hmC) and H3K4me3. The COMPASS-like H3K4 methyltransferase Mll2 is the major H3K4me3 methylase at the Zfp281-regulated L1s and required for their proper expression. Our studies also reveal that Zfp281 functions partially through recruiting the L1 regulators DNA hydroxymethylase Tet1 and Sin3A, and restricting Mll2 at these active L1s, leading to their balanced expression. In summary, our data indicate an instrumental role of Zfp281 in suppressing the young active L1s in mouse ES cells. Oxford University Press 2017-12-01 2017-09-25 /pmc/articles/PMC5716208/ /pubmed/29036642 http://dx.doi.org/10.1093/nar/gkx841 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Dai, Qian Shen, Yang Wang, Yan Wang, Xin Francisco, Joel Celio Luo, Zhuojuan Lin, Chengqi Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells |
title | Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells |
title_full | Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells |
title_fullStr | Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells |
title_full_unstemmed | Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells |
title_short | Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells |
title_sort | striking a balance: regulation of transposable elements by zfp281 and mll2 in mouse embryonic stem cells |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716208/ https://www.ncbi.nlm.nih.gov/pubmed/29036642 http://dx.doi.org/10.1093/nar/gkx841 |
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