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DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila

DNMT3L is an important epigenetic regulator in mammals, integrating DNA methylation and histone modification based epigenetic circuits. Here we show DNMT3L to be a part of the machinery that enables inheritance of epigenetic modifications from one generation to the next. Ectopic expression of DNMT3L...

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Autores principales: Basu, Amitava, Tomar, Archana, Dasari, Vasanthi, Mishra, Rakesh Kumar, Khosla, Sanjeev
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726149/
https://www.ncbi.nlm.nih.gov/pubmed/26795243
http://dx.doi.org/10.1038/srep19572
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author Basu, Amitava
Tomar, Archana
Dasari, Vasanthi
Mishra, Rakesh Kumar
Khosla, Sanjeev
author_facet Basu, Amitava
Tomar, Archana
Dasari, Vasanthi
Mishra, Rakesh Kumar
Khosla, Sanjeev
author_sort Basu, Amitava
collection PubMed
description DNMT3L is an important epigenetic regulator in mammals, integrating DNA methylation and histone modification based epigenetic circuits. Here we show DNMT3L to be a part of the machinery that enables inheritance of epigenetic modifications from one generation to the next. Ectopic expression of DNMT3L in Drosophila, which lacks DNMT3L and its normal interacting partners DNMT3A and DNMT3B, lead to nuclear reprogramming that was gradual and progressive, resulting in melanotic tumors that were observed only when these flies were maintained for five generations. This global gene expression misregulation was accompanied by aberrations in the levels of H3K4me(3) and H3K36me(3), globally as well as at specific gene promoters. The levels of these epigenetic aberrations (epimutations) also increased progressively across successive generations. The accumulation and inheritance of epimutations across multiple generations recapitulates the important role of DNMT3L in intergenerational epigenetic inheritance in mammals.
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spelling pubmed-47261492016-01-27 DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila Basu, Amitava Tomar, Archana Dasari, Vasanthi Mishra, Rakesh Kumar Khosla, Sanjeev Sci Rep Article DNMT3L is an important epigenetic regulator in mammals, integrating DNA methylation and histone modification based epigenetic circuits. Here we show DNMT3L to be a part of the machinery that enables inheritance of epigenetic modifications from one generation to the next. Ectopic expression of DNMT3L in Drosophila, which lacks DNMT3L and its normal interacting partners DNMT3A and DNMT3B, lead to nuclear reprogramming that was gradual and progressive, resulting in melanotic tumors that were observed only when these flies were maintained for five generations. This global gene expression misregulation was accompanied by aberrations in the levels of H3K4me(3) and H3K36me(3), globally as well as at specific gene promoters. The levels of these epigenetic aberrations (epimutations) also increased progressively across successive generations. The accumulation and inheritance of epimutations across multiple generations recapitulates the important role of DNMT3L in intergenerational epigenetic inheritance in mammals. Nature Publishing Group 2016-01-22 /pmc/articles/PMC4726149/ /pubmed/26795243 http://dx.doi.org/10.1038/srep19572 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Basu, Amitava
Tomar, Archana
Dasari, Vasanthi
Mishra, Rakesh Kumar
Khosla, Sanjeev
DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila
title DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila
title_full DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila
title_fullStr DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila
title_full_unstemmed DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila
title_short DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila
title_sort dnmt3l enables accumulation and inheritance of epimutations in transgenic drosophila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726149/
https://www.ncbi.nlm.nih.gov/pubmed/26795243
http://dx.doi.org/10.1038/srep19572
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