DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila

Basu, Amitava (2015) DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila. Scientific Reports, 22 (6). pp. 1-16.

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Abstract

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 H3K4me3 and H3K36me3, 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.

Item Type: Article
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 21 Mar 2016 09:10
Last Modified: 21 Mar 2016 09:10
URI: http://eprints.manipal.edu/id/eprint/145614

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