title: DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila.
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.
authors.affiliation: Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India.|Graduate Studies, Manipal University, Manipal, India.
authors.forename: Amitava
authors.initials: A
authors.lastname: Basu
authors.affiliation: Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Tomar
authors.affiliation: Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Hyderabad, India.
authors.forename: Vasanthi
authors.initials: V
authors.lastname: Dasari
authors.affiliation: Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Hyderabad, India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Mishra
authors.affiliation: Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Khosla
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D047369:Chromatin Immunoprecipitation; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics*; D044127:Epigenesis, Genetic; D005123:Eye / Q000473:pathology; D017344:Genes, Insect; D006657:Histones / Q000378:metabolism; D040582:Inheritance Patterns / Q000235:genetics*; D007814:Larva / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D008745:Methylation; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010641:Phenotype; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014921:Wings, Animal / Q000033:anatomy & histology
chemical_list: D006657:Histones; D004248:DNA (Cytosine-5-)-Methyltransferases