ArticleAmerican journal of human genetics2013
A regulatory path associated with X-linked intellectual disability and epilepsy links KDM5C to the polyalanine expansions in ARX.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- Cannabidiol attenuates epileptic phenotype and increases survival in a mouse model of developmental and epileptic encephalopathy type 1.Epilepsia · 2025Article
- Chromatin modifiers in neurodevelopment.Frontiers in molecular neuroscience · 2025Review
- Epigenetic Mechanisms in the Pathophysiology and Progression of Epilepsy: A Comprehensive Review of Experimental and Clinical Studies.Current neuropharmacology · 2025Review
- The Aggravation of Neuropsychiatric Symptoms in the Offspring of a Korean Family with Intellectual Disability and Developmental Delay Caused by a NovelInternational journal of molecular sciences · 2024Article
- Sex-biased gene expression during neural differentiation of human embryonic stem cells.Frontiers in cell and developmental biology · 2024Article
- Cortical interneuron development is affected in 4H leukodystrophy.Brain : a journal of neurology · 2023Article
- Clocking Epilepsies: A Chronomodulated Strategy-Based Therapy for Rhythmic Seizures.International journal of molecular sciences · 2023Review
- The Chromatin-Oxygen Sensor GeneInternational journal of molecular sciences · 2022Article
- Deregulation of microtubule organization and RNA metabolism in Arx models for lissencephaly and developmental epileptic encephalopathy.Human molecular genetics · 2022Article
- Further Delineation of Duplications ofInternational journal of molecular sciences · 2022Review
- Article
- The emerging role of chromatin remodelers in neurodevelopmental disorders: a developmental perspective.Cellular and molecular life sciences : CMLS · 2021Review
- Therapeutic effect of a histone demethylase inhibitor in Parkinson's disease.Cell death & disease · 2020Article
- Review
- Histone demethylase KDM5C is a SAHA-sensitive central hub at the crossroads of transcriptional axes involved in multiple neurodevelopmental disorders.Human molecular genetics · 2019Article
- Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.American journal of human genetics · 2019Article
- Histone Lysine Methylation and Neurodevelopmental Disorders.International journal of molecular sciences · 2017Review
- The Diathesis-Epilepsy Model: How Past Events Impact the Development of Epilepsy and Comorbidities.Cold Spring Harbor perspectives in medicine · 2016Review
- A Mouse Model of X-linked Intellectual Disability Associated with Impaired Removal of Histone Methylation.Cell reports · 2016Article
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Authors and funding
13 authors at 4 institutions in 3 countries.
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Abstract
Intellectual disability (ID) and epilepsy often occur together and have a dramatic impact on the development and quality of life of the affected children. Polyalanine (polyA)-expansion-encoding mutations of aristaless-related homeobox (ARX) cause a spectrum of X-linked ID (XLID) diseases and chronic epilepsy, including infantile spasms. We show that lysine-specific demethylase 5C (KDM5C), a gene known to be mutated in XLID-affected children and involved in chromatin remodeling, is directly regulated by ARX through the binding in a conserved noncoding element. We have studied altered ARX carrying various polyA elongations in individuals with XLID and/or epilepsy. The changes in polyA repeats cause hypomorphic ARX alterations, which exhibit a decreased trans-activity and reduced, but not abolished, binding to the KDM5C regulatory region. The altered functioning of the mutants tested is likely to correlate with the severity of XLID and/or epilepsy. By quantitative RT-PCR, we observed a dramatic Kdm5c mRNA downregulation in murine Arx-knockout embryonic and neural stem cells. Such Kdm5c mRNA diminution led to a severe decrease in the KDM5C content during in vitro neuronal differentiation, which inversely correlated with an increase in H3K4me3 signal. We established that ARX polyA alterations damage the regulation of KDM5C expression, and we propose a potential ARX-dependent path acting via chromatin remodeling.
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