ArticleHuman molecular genetics2015
Epigenetic dysregulation of hairy and enhancer of split 4 (HES4) is associated with striatal degeneration in postmortem Huntington brains.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Improving reproducibility of differentially expressed genes in single-cell transcriptomic studies of neurodegenerative diseases through meta-analysis.Nature communications · 2025Pooled it
- The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review.PloS one · 2016Pooled it
- Diagnostic and Prognostic Value of Epigenetic Markers in Neurological Diseases. A Narrative Review.Cellular and molecular neurobiology · 2026Review
- Review
- A Reproducibility Focused Meta-Analysis Method for Single-Cell Transcriptomic Case-Control Studies Uncovers Robust Differentially Expressed Genes.bioRxiv : the preprint server for biology · 2025Article
- Contrasting genetic predisposition and diagnosis in psychiatric disorders: A multi-omic single-nucleus analysis of the human OFC.Science advances · 2025Article
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- Article
- Single-nuclei transcriptome analysis of Huntington disease iPSC and mouse astrocytes implicates maturation and functional deficits.iScience · 2023Article
- Review
- Dementia with Lewy bodies post-mortem brains reveal differentially methylated CpG sites with biomarker potential.Communications biology · 2022Article
- Epigenetic Changes in Prion and Prion-like Neurodegenerative Diseases: Recent Advances, Potential as Biomarkers, and Future Perspectives.International journal of molecular sciences · 2022Review
- DNA Methylation: A Promising Approach in Management of Alzheimer's Disease and Other Neurodegenerative Disorders.Biology · 2022Review
- Protein disulfide isomerase A6 promotes the repair of injured nerve through interactions with spastin.Frontiers in molecular neuroscience · 2022Article
- Huntington's disease iPSC models-using human patient cells to understand the pathology caused by expanded CAG repeats.Faculty reviews · 2022Review
- Exercise Modifies the Transcriptional Regulatory Features of Monocytes in Alzheimer's Patients: A Multi-Omics Integration Analysis Based on Single Cell Technology.Frontiers in aging neuroscience · 2022Article
- Neurodegenerative movement disorders: An epigenetics perspective and promise for the future.Neuropathology and applied neurobiology · 2021Review
- Epigenetic regulation in Huntington's disease.Neurochemistry international · 2021Review
- Histone Methylation Regulation in Neurodegenerative Disorders.International journal of molecular sciences · 2021Review
- Age-related and disease locus-specific mechanisms contribute to early remodelling of chromatin structure in Huntington's disease mice.Nature communications · 2021Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
To investigate epigenetic contributions to Huntington's disease (HD) pathogenesis, we carried out genome-wide mapping of the transcriptional mark, trimethyl-histone H3-lysine 4 (H3K4me3) in neuronal nuclei extracted from prefrontal cortex of HD cases and controls using chromatin immunoprecipitation followed by deep-sequencing. Neuron-specific mapping of the genome-wide distribution of H3K4me3 revealed 136 differentially enriched loci associated with genes implicated in neuronal development and neurodegeneration, including GPR3, TMEM106B, PDIA6 and the Notch signaling genes hairy and enhancer of split 4 (HES4) and JAGGED2, supporting the view that the neuronal epigenome is affected in HD. Importantly, loss of H3K4me3 at CpG-rich sequences on the HES4 promoter was associated with excessive DNA methylation, reduced binding of nuclear proteins to the methylated region and altered expression of HES4 and HES4 targeted genes MASH1 and P21 involved in striatal development. Moreover, hypermethylation of HES4 promoter sequences was strikingly correlated with measures of striatal degeneration and age-of-onset in a cohort of 25 HD brains (r = 0.56, P = 0.006). Lastly, shRNA knockdown of HES4 in human neuroblastoma cells altered MASH1 and P21 mRNA expression and markedly increased mutated HTT-induced aggregates and cell death. These findings, taken together, suggest that epigenetic dysregulation of HES4 could play a critical role in modifying HD disease pathogenesis and severity.
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