ArticleTranslational psychiatry2014
Elevated 5-hydroxymethylcytosine in the Engrailed-2 (EN-2) promoter is associated with increased gene expression and decreased MeCP2 binding in autism cerebellum.
Article in Translational psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Case-control meta-analysis of blood DNA methylation and autism spectrum disorder.Molecular autism · 2018Pooled it
- Review
- Autism Spectrum Disorder: The Cerebellum, Genes, and Pathways.Neurology international · 2025Review
- A comprehensive review of GABA in autism spectrum disorders: associations, mechanisms, and therapeutic implications.Frontiers in psychiatry · 2025Review
- Unveiling the mechanistic nexus: how micronutrient enrichment shapes brain function, and cognitive health.Frontiers in molecular biosciences · 2025Review
- Epigenetics of Genes Preferentially Expressed in Dissimilar Cell Populations: Myoblasts and Cerebellum.Epigenomes · 2024Article
- Intercontinental insights into autism spectrum disorder: a synthesis of environmental influences and DNA methylation.Environmental epigenetics · 2024Review
- Exploring the epigenetic landscape: The role of 5-hydroxymethylcytosine in neurodevelopmental disorders.Cambridge prisms. Precision medicine · 2024Review
- 5-Methylcytosine and 5-Hydroxymethylcytosine in Scrapie-Infected Sheep and Mouse Brain Tissues.International journal of molecular sciences · 2023Article
- A pilot investigation of differential hydroxymethylation levels in patient-derived neural stem cells implicates altered cortical development in bipolar disorder.Frontiers in psychiatry · 2023Article
- GABAergic System Dysfunction in Autism Spectrum Disorders.Frontiers in cell and developmental biology · 2021Review
- Aberrant Somatosensory Processing and Connectivity in Mice LackingThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- DNA Methylation and Susceptibility to Autism Spectrum Disorder.Annual review of medicine · 2019Review
- Sensory Abnormalities in Autism Spectrum Disorders: A Focus on the Tactile Domain, From Genetic Mouse Models to the Clinic.Frontiers in psychiatry · 2019Review
- Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability.Human genetics · 2018Article
- Association of Bisphenol A Exposure with LINE-1 Hydroxymethylation in Human Semen.International journal of environmental research and public health · 2018Article
- Epigenetics and cerebral organoids: promising directions in autism spectrum disorders.Translational psychiatry · 2018Review
- Clinical Phenotypes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients.Frontiers in neuroanatomy · 2018Article
- Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2017Article
- Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder.Nature communications · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Epigenetic mechanisms regulate programmed gene expression during prenatal neurogenesis and serve as a mediator between genetics and environment in postnatal life. The recent discovery of 5-hydroxymethylcytosine (5-hmC), with highest concentration in the brain, has added a new dimension to epigenetic regulation of neurogenesis and the development of complex behavior disorders. Here, we take a candidate gene approach to define the role 5-hmC in Engrailed-2 (EN-2) gene expression in the autism cerebellum. The EN-2 homeobox transcription factor, previously implicated in autism, is essential for normal cerebellar patterning and development. We previously reported EN-2 overexpression associated with promoter DNA hypermethylation in the autism cerebellum but because traditional DNA methylation methodology cannot distinguish 5-methylcytosine (5-mC) from 5-hmC, we now extend our investigation by quantifying global and gene-specific 5-mC and 5-hmC. Globally, 5-hmC was significantly increased in the autism cerebellum and accompanied by increases in the expression of de novo methyltransferases DNMT3A and DNMT3B, ten-eleven translocase genes TET1 and TET3, and in 8-oxo-deoxyguanosine (8-oxo-dG) content, a marker of oxidative DNA damage. Within the EN-2 promoter, there was a significant positive correlation between 5-hmC content and EN-2 gene expression. Based on reports of reduced MeCP2 affinity for 5-hmC, MeCP2 binding studies in the EN-2 promoter revealed a significant decrease in repressive MeCP2 binding that may contribute to the aberrant overexpression of EN-2. Because normal cerebellar development depends on perinatal EN-2 downregulation, the sustained postnatal overexpression suggests that a critical window of cerebellar development may have been missed in some individuals with autism with downstream developmental consequences. Epigenetic regulation of the programmed on-off switches in gene expression that occur at birth and during early brain development warrants further investigation.
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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.