ArticleHuman molecular genetics2016
Global hypermethylation in fetal cortex of Down syndrome due to DNMT3L overexpression.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- A modified CRISPR/Cas9 approach in silencing the triplication in Down syndrome: A treatment path XISTs.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Hallmarks of Aneuploidy in Cancer and Congenital Syndromes.Annual review of genomics and human genetics · 2025Review
- DNA methylation biomarkers of intellectual/developmental disability across the lifespan.Journal of neurodevelopmental disorders · 2025Review
- Carcinogenesis trajectories.Frontiers in cell and developmental biology · 2025Article
- Consequences of trisomy 21 for brain development in Down syndrome.Nature reviews. Neuroscience · 2024Review
- A single-cell transcriptome atlas of human euploid and aneuploid blastocysts.Nature genetics · 2024Article
- Epigenomic signatures reveal mechanistic clues and predictive markers for autism spectrum disorder.Molecular psychiatry · 2023Review
- Dopamine-related oxidative stress and mitochondrial dysfunction in dopaminergic neurons differentiated from deciduous teeth-derived stem cells of children with Down syndrome.FASEB bioAdvances · 2022Article
- Effects of aneuploidy on cell behaviour and function.Nature reviews. Molecular cell biology · 2022Review
- Developmental Neuropathology and Neurodegeneration of Down Syndrome: Current Knowledge in Humans.Frontiers in cell and developmental biology · 2022Review
- Role of long non-coding RNAs in Down syndrome patients: a transcriptome analysis study.Human cell · 2021Article
- Article
- Stable DNMT3L overexpression in SH-SY5Y neurons recreates a facet of the genome-wide Down syndrome DNA methylation signature.Epigenetics & chromatin · 2021Article
- The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.Nature communications · 2021Article
- Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles.Human molecular genetics · 2021Article
- Impact of the Olig Family on Neurodevelopmental Disorders.Frontiers in neuroscience · 2021Review
- Rethinking Intellectual Disability from Neuro- to Astro-Pathology.International journal of molecular sciences · 2020Review
- Identification of fetal unmodified and 5-hydroxymethylated CG sites in maternal cell-free DNA for non-invasive prenatal testing.Clinical epigenetics · 2020Article
- The BACH1/Nrf2 Axis in Brain in Down Syndrome and Transition to Alzheimer Disease-Like Neuropathology and Dementia.Antioxidants (Basel, Switzerland) · 2020Review
- Human iPSC-derived Down syndrome astrocytes display genome-wide perturbations in gene expression, an altered adhesion profile, and increased cellular dynamics.Human molecular genetics · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Down syndrome (DS) is caused by a triplication of chromosome 21 (HSA21). Increased oxidative stress, decreased neurogenesis and synaptic dysfunction from HSA21 gene overexpression are thought to cause mental retardation, dementia and seizure in this disorder. Recent epigenetic studies have raised the possibility that DNA methylation has significant effects on DS neurodevelopment. Here, we performed methylome profiling in normal and DS fetal cortices and observed a significant hypermethylation in ∼4% of probes in the DS samples compared with age-matched normals. The probes with differential methylation were distributed across all chromosomes, with no enrichment on HSA21. Functional annotation and pathway analyses showed that genes in the ubiquitination pathway were significantly altered, including: BRCA1, TSPYL5 and PEX10 HSA21 located DNMT3L was overexpressed in DS neuroprogenitors, and this overexpression increased the promoter methylation of TSPYL5 potentially through DNMT3B, and decreased its mRNA expression. DNMT3L overexpression also increased mRNA levels for TP53 and APP, effectors of TSPYL5 Furthermore, DNMT3L overexpression increased APP and PSD95 expression in differentiating neurons, whereas DNMT3LshRNA could partially rescue the APP and PSD95 up-regulation in DS cells. These results provide some of the first mechanistic insights into causes for epigenetic changes in DS, leading to modification of genes relevant for the DS neural endophenotype.
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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.