ArticleHuman molecular genetics2009
DNA hypomethylation restricted to the murine forebrain induces cortical degeneration and impairs postnatal neuronal maturation.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 176 citations in OpenAlex.
- Whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN).Scientific reports · 2021Trial
- Neuronal activity-dependent gene dysregulation inAmerican journal of physiology. Cell physiology · 2025Article
- Glial reactivity and cognitive decline follow chronic heterochromatin loss in neurons.Nature communications · 2025Article
- DNMT1-mediated regulation of somatostatin-positive interneuron migration impacts cortical architecture and function.Nature communications · 2025Article
- Dysfunctional one-carbon metabolism identifies vitamins BCell reports. Medicine · 2025Article
- DNMT3b-mediated CpA methylation facilitates REST binding and gene silencing and exacerbates hippocampal demyelination in diabetic mice.The Journal of biological chemistry · 2025Article
- Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC.Frontiers in pharmacology · 2025Review
- Review
- Making Ramón y Cajal proud: Development of cell identity and diversity in the cerebral cortex.Neuron · 2024Review
- Review
- Mutations in human DNA methyltransferase DNMT1 induce specific genome-wide epigenomic and transcriptomic changes in neurodevelopment.Human molecular genetics · 2023Article
- Review
- Mechanisms of abnormal adult hippocampal neurogenesis in Alzheimer's disease.Frontiers in neuroscience · 2023Review
- Evidence that direct inhibition of transcription factor binding is the prevailing mode of gene and repeat repression by DNA methylation.Nature genetics · 2022Article
- Dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm.Nature communications · 2022Article
- Genetic Studies on Mammalian DNA Methyltransferases.Advances in experimental medicine and biology · 2022Article
- Role of DNMTs in the Brain.Advances in experimental medicine and biology · 2022Review
- Epigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease.International journal of molecular sciences · 2021Review
- The Epigenome in Neurodevelopmental Disorders.Frontiers in neuroscience · 2021Review
- High Methionine Diet-Induced Alzheimer's Disease like Symptoms Are Accompanied by 5-Methylcytosine Elevated Levels in the Brain.Behavioural neurology · 2021Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
DNA methylation is a major epigenetic factor regulating genome reprogramming, cell differentiation and developmental gene expression. To understand the role of DNA methylation in central nervous system (CNS) neurons, we generated conditional Dnmt1 mutant mice that possess approximately 90% hypomethylated cortical and hippocampal cells in the dorsal forebrain from E13.5 on. The mutant mice were viable with a normal lifespan, but displayed severe neuronal cell death between E14.5 and three weeks postnatally. Accompanied with the striking cortical and hippocampal degeneration, adult mutant mice exhibited neurobehavioral defects in learning and memory in adulthood. Unexpectedly, a fraction of Dnmt1(-/-) cortical neurons survived throughout postnatal development, so that the residual cortex in mutant mice contained 20-30% of hypomethylated neurons across the lifespan. Hypomethylated excitatory neurons exhibited multiple defects in postnatal maturation including abnormal dendritic arborization and impaired neuronal excitability. The mutant phenotypes are coupled with deregulation of those genes involved in neuronal layer-specification, cell death and the function of ion channels. Our results suggest that DNA methylation, through its role in modulating neuronal gene expression, plays multiple roles in regulating cell survival and neuronal maturation in the CNS.
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