DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila

Scientific Reports
Amitava BasuSanjeev Khosla

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.

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Citations

Sep 27, 2018·The Journal of Experimental Biology·Varada AbhyankarGirish S Ratnaparkhi

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Methods Mentioned

BETA
transgenic
immunoprecipitation
ChIP
PCR

Software Mentioned

modENCODE
BEDtools
Transcriptome Analysis Console ( TAC )
RMA
DNMT3L
sketch
DAVID Bioinformatics Resources
Affymetrix Expression Console
Affymetrix
Affymetrix Transcriptome Analysis Console ( TAC )

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