Researchers at the Garvan Institute of Medical Research have uncovered a new form of DNA modification in the genome of zebrafish.
Methylation of cytosine within CG dinucleotides regions is the most abundant DNA modification in vertebrate genomes. CG methylation (mCG) is found in all vertebrate cell types. It is known to be involved in long-term gene silencing processes. In vertebrates, ∼80% of all genomic CG dinucleotides are methylated. Methylation of other cytosine dinucleotides are present at much lower levels. They are most commonly found in mammalian embryonic stem cells (ESCs) and in the brain. In mammals, non-CG methylation (mCH) is often found at CAC trinucleotides in the nervous system, where it is associated with transcriptional repression. However, in ESCs, it is often found at CAG trinucleotides where it positively correlates with transcription. Additionally, CAC methylation appears to be a conserved feature of adult vertebrate brains.
In a study, published in Nucleic Acids Research, researchers performed whole genome bisulphite sequencing and enzymatic methylation sequencing to investigate mCH further. The team uncovered a novel form of mCH, which occurred within the TGCT tetranucleotides at zebrafish satellite repeats. They found that it was present at significantly higher levels than any other mCH type. TGCT methylation is inherited from both male and female gametes. It is then remodelled during the mid-blastula transition and re-established during gastrulation.
They also found that this form of mCH is deposited by an actinopterygian-specific DNMT enzyme – Dnmt3ba. This modification is specifically associated with the repressive histone mark H3H9me3, suggesting a link between mCH and heterochromatin.
Zebrafish are vertebrate animals that share an evolutionary ancestor with humans ~400 million years ago. They share 70% of our genes, making them a useful model for studying the effects of human genes. The team’s discovery in zebrafish is significant because it will enable researchers to selectively manipulate this form of methylation in a model organism. It also means researchers can alter the levels of Dnmt3ba and see what happens when different forms of methylation are removed.
Dr Ozren Bogdanovic, who heads the Developmental Epigenomics Lab at Garvan, stated:
“This could greatly facilitate our understanding of how changes in atypical methylation patterns affect specific tissues such as the brain, to gain further insights into the molecular mechanisms of neurodevelopmental disorders.”
Image credit: By GarryKillian – www.freepik.com