Developmental remodelling of non-CG methylation at satellite DNA repeats

Abstract In vertebrates, DNA methylation predominantly occurs at CG dinucleotides however, widespread non-CG methylation (mCH) has been reported in mammalian embryonic stem cells and in the brain. In mammals, mCH is found at CAC trinucleotides in the nervous system, where it is associated with trans...

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Bibliographic Details
Published in:Nucleic acids research 2020-12, Vol.48 (22), p.12675-12688
Main Authors: Ross, Samuel E, Angeloni, Allegra, Geng, Fan-Suo, de Mendoza, Alex, Bogdanovic, Ozren
Format: Article
Language:English
Subjects:
Animals
Blastocyst - metabolism
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA Methylation - genetics
DNA, Satellite - genetics
Embryonic Stem Cells - metabolism
Gene regulation, Chromatin and Epigenetics
Heterochromatin
Histones - genetics
Mosaicism
Protein Processing, Post-Translational - genetics
Repetitive Sequences, Nucleic Acid - genetics
Zebrafish - genetics
Zebrafish - growth & development
Zebrafish Proteins - genetics
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Summary:Abstract In vertebrates, DNA methylation predominantly occurs at CG dinucleotides however, widespread non-CG methylation (mCH) has been reported in mammalian embryonic stem cells and in the brain. In mammals, mCH is found at CAC trinucleotides in the nervous system, where it is associated with transcriptional repression, and at CAG trinucleotides in embryonic stem cells, where it positively correlates with transcription. Moreover, CAC methylation appears to be a conserved feature of adult vertebrate brains. Unlike any of those methylation signatures, here we describe a novel form of mCH that occurs in the TGCT context within zebrafish mosaic satellite repeats. TGCT methylation is inherited from both male and female gametes, remodelled during mid-blastula transition, and re-established during gastrulation in all embryonic layers. Moreover, we identify DNA methyltransferase 3ba (Dnmt3ba) as the primary enzyme responsible for the deposition of this mCH mark. Finally, we observe that TGCT-methylated repeats are specifically associated with H3K9me3-marked heterochromatin suggestive of a functional interplay between these two gene-regulatory marks. Altogether, this work provides insight into a novel form of vertebrate mCH and highlights the substrate diversity of vertebrate DNA methyltransferases.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkaa1135