ArticleHuman molecular genetics2018
Systematic genetic interaction studies identify histone demethylase Utx as potential target for ameliorating Huntington's disease.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Altered huntingtin-chromatin interactions predict transcriptional and epigenetic changes in Huntington's disease.Disease models & mechanisms · 2025Article
- G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.Medicinal research reviews · 2025Review
- Roles of Kdm6a and Kdm6b in Regulation of Mammalian Neural Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration.Biology · 2024Review
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
- The ubiquitin thioesterase YOD1 ameliorates mutant Huntingtin induced pathology in Drosophila.Scientific reports · 2023Article
- Involvement of the H3.3 Histone Variant in the Epigenetic Regulation of Gene Expression in the Nervous System, in Both Physiological and Pathological Conditions.International journal of molecular sciences · 2023Review
- The Dynamic and Crucial Role of the Arginine Methylproteome in Myoblast Cell Differentiation.International journal of molecular sciences · 2023Article
- Longevity-Associated Variant of BPIFB4 Confers Neuroprotection in the STHdh Cell Model of Huntington Disease.International journal of molecular sciences · 2022Article
- Acetylation State of Lysine 14 of Histone H3.3 Affects Mutant Huntingtin Induced Pathogenesis.International journal of molecular sciences · 2022Article
- Epigenetic Changes in Prion and Prion-like Neurodegenerative Diseases: Recent Advances, Potential as Biomarkers, and Future Perspectives.International journal of molecular sciences · 2022Review
- Despite its sequence identity with canonical H4, Drosophila H4r product is enriched at specific chromatin regions.Scientific reports · 2022Article
- Mutant Huntingtin Protein Interaction Map Implicates Dysregulation of Multiple Cellular Pathways in Neurodegeneration of Huntington's Disease.Journal of Huntington's disease · 2022Article
- DNA Methylation in Huntington's Disease.International journal of molecular sciences · 2021Review
- Epigenetic regulation in Huntington's disease.Neurochemistry international · 2021Review
- IDO and Kynurenine Metabolites in Peripheral and CNS Disorders.Frontiers in immunology · 2020Review
- Histone methylation in Huntington's disease: are bivalent promoters the critical targets?Neural regeneration research · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by alterations in the huntingtin gene (htt). Transcriptional dysregulation is an early event in HD progression. Protein acetylation and methylation particularly on histones regulates chromatin structure thereby preventing or facilitating transcription. Although protein acetylation has been found to affect HD symptoms, little is known about the potential role of protein methylation in HD pathology. In recent years, a series of proteins have been described that are responsible for methylating and demethylating histones as well as other proteins. We carried out systematic genetic interaction studies testing lysine and arginine methylases and demethylases in a Drosophila melanogaster HD model. We found that modulating methylation enzymes that typically affect histone positions H3K4, H3K36 or H3K79 had varying effects on HD pathology while modulating ones that typically affect constitutive heterochromatin marks at H3K9 and H4K20 generally had limited impact on HD pathology. In contrast, modulating enzymes acting on the facultative heterochromatin mark at H3K27 had specific effects on HD pathology, with reduction of the demethylase Utx rescuing HTT-induced pathology while reducing Polycomb Repressive Complex2 core methylase components led to more aggressive pathology. Further exploration of the mechanism underlying the methylation-specific interactions suggest that these lysine and arginine methylases and demethylases are likely exerting their influence through non-histone targets. These results highlight a novel therapeutic approach for HD in the form of Utx inhibition.
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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.