Developmental Accumulation of Gene Body and Transposon Non-CpG Methylation in the Zebrafish Brain
Open Access
- 4 March 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
DNA methylation predominantly occurs at CG dinucleotides in vertebrate genomes; however, non-CG methylation (mCH) is also detectable in vertebrate tissues, most notably in the nervous system. In mammals it is well established that mCH is targeted to CAC trinucleotides by DNMT3A during nervous system development where it is enriched in gene bodies and associated with transcriptional repression. Nevertheless, the conservation of developmental mCH accumulation and its deposition by DNMT3A is largely unexplored and has yet to be functionally demonstrated in other vertebrates. In this study, by analyzing DNA methylomes and transcriptomes of zebrafish brains, we identified enrichment of mCH at CAC trinucleotides (mCAC) at defined transposon motifs as well as in developmentally downregulated genes associated with developmental and neural functions. We further generated and analyzed DNA methylomes and transcriptomes of developing zebrafish larvae and demonstrated that, like in mammals, mCH accumulates during post-embryonic brain development. Finally, by employing CRISPR/Cas9 technology, we unraveled a conserved role for Dnmt3a enzymes in developmental mCAC deposition. Overall, this work demonstrates the evolutionary conservation of developmental mCH dynamics and highlights the potential of zebrafish as a model to study mCH regulation and function during normal and perturbed development.Keywords
Funding Information
- Australian Research Council
This publication has 64 references indexed in Scilit:
- MeCP2 Represses Enhancers through Chromosome Topology-Associated DNA MethylationMolecular Cell, 2020
- MeCP2 Represses the Rate of Transcriptional Initiation of Highly Methylated Long GenesMolecular Cell, 2019
- Retrotransposon-induced mosaicism in the neural genomeOpen Biology, 2018
- Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderlyNature Communications, 2018
- WALT: fast and accurate read mapping for bisulfite sequencingBioinformatics, 2016
- Active DNA demethylation at enhancers during the vertebrate phylotypic periodNature Genetics, 2016
- MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndromeProceedings of the National Academy of Sciences of the United States of America, 2015
- Trimmomatic: a flexible trimmer for Illumina sequence dataBioinformatics, 2014
- In Vivo Control of CpG and Non-CpG DNA Methylation by DNA MethyltransferasesPLoS Genetics, 2012
- DNA methylation patterns and epigenetic memoryGenes & Development, 2002