ArticleNature ecology & evolution2021
The emergence of the brain non-CpG methylation system in vertebrates.
Article in Nature ecology & evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 120 citations in OpenAlex.
- DNA methylation signatures of bilateral hippocampal volume, asymmetry and atrophy: a cross-omics analysis in the general population.EBioMedicine · 2026Pooled it
- A systematic review on the contribution of DNA methylation to hearing loss.Clinical epigenetics · 2024Pooled it
- Single-cell analysis of the epigenome and 3D chromatin architecture in the human retina.Science advances · 2026Article
- Epigenetic signatures of migratory orientation in a songbird hybrid zone.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Article
- The molecular evolution of vertebrate organs.Nature ecology & evolution · 2026Review
- Distinct cellular DNA methylation mechanisms underlie common and rare genetic risk for brain disorders.bioRxiv : the preprint server for biology · 2026Article
- Targeting epigenetic remodeling of the blood-brain barrier: current knowledge for drug therapy.Epigenomics · 2026Review
- Multimodal bHLH-PAS DNA binding controls specificity and drives obesity.Nucleic acids research · 2026Article
- MethPy: a new software for analyzing non-CpG methylation after bisulfite assay and Sanger sequencing.Scientific reports · 2025Article
- Methylome Profiling of a Deuterostome Invertebrate Using Oxford Nanopore Technology (ONT).Molecular ecology resources · 2025Article
- Non-CG DNA methylation in animal genomes.Nature genetics · 2025Review
- Steroid hormone-mediated epigenetic programming during puberty: uncovering links to depression.Epigenomics · 2025Review
- Simultaneous RNA Sequencing and DNA Methylation Profiling Reveals Neural Mechanisms That Regulate Sensitive Period Behavioral Learning.Genes, brain, and behavior · 2025Article
- Repressive Cytosine Methylation is a Marker of Viral Gene Transfer Across Divergent Eukaryotes.Molecular biology and evolution · 2025Article
- Aere perennius: how chromatin fidelity is maintained and lost in disease.NAR molecular medicine · 2025Review
- MeCP2 and non-CG DNA methylation stabilize the expression of long genes that distinguish closely related neuron types.Nature neuroscience · 2025Article
- The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment.Current oncology (Toronto, Ont.) · 2025Review
- Chromatin modifiers in neurodevelopment.Frontiers in molecular neuroscience · 2025Review
- Type-2 diabetes epigenetic biomarkers: present status and future directions for global and Indigenous health.Frontiers in molecular biosciences · 2025Review
- DNA methylation in mammalian development and disease.Nature reviews. Genetics · 2025Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 9 institutions in 6 countries.
Funding
Abstract
Mammalian brains feature exceptionally high levels of non-CpG DNA methylation alongside the canonical form of CpG methylation. Non-CpG methylation plays a critical regulatory role in cognitive function, which is mediated by the binding of MeCP2, the transcriptional regulator that when mutated causes Rett syndrome. However, it is unclear whether the non-CpG neural methylation system is restricted to mammalian species with complex cognitive abilities or has deeper evolutionary origins. To test this, we investigated brain DNA methylation across 12 distantly related animal lineages, revealing that non-CpG methylation is restricted to vertebrates. We discovered that in vertebrates, non-CpG methylation is enriched within a highly conserved set of developmental genes transcriptionally repressed in adult brains, indicating that it demarcates a deeply conserved regulatory program. We also found that the writer of non-CpG methylation, DNMT3A, and the reader, MeCP2, originated at the onset of vertebrates as a result of the ancestral vertebrate whole-genome duplication. Together, we demonstrate how this novel layer of epigenetic information assembled at the root of vertebrates and gained new regulatory roles independent of the ancestral form of the canonical CpG methylation. This suggests that the emergence of non-CpG methylation may have fostered the evolution of sophisticated cognitive abilities found in the vertebrate lineage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.