biostudies-literatureYousefian-Jazi AKIST GrantNINDS NIH HHSNational Research FoundationNIH R01Korea Dementia Research Project Grant16https://www.ebi.ac.uk/biostudies/studies/S-EPMC11806887biostudies-literatureUnknown20(1)<h4>Background</h4>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, leading to progressive paralysis. Both genetic alterations and epigenetic modifications contribute to neuronal dysfunction in the pathogenesis of ALS. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear.<h4>Methods</h4>Convolutional neural network was used to identify an ALS-associated SNP located in the intronic region of MEF2C (rs304152), residing in a putative enhancer element. To examine the alteration of MEF2C transcription by the SNP, we generated HEK293T cells carrying the major or minor allele by CRISPR-Cas9. To verify the role of MEF2C-knockdowMolecular neurodegenerationLoss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice.PMC118068872E30954R01 NS109537HU23C02172022R1A2C3013138R01NS109537Hwang HLee JLee KHyeon SJRyu HNguyen PTTPark UStein TDKim SChoi SHYousefian-Jazi ALim GKim YRhim HRyu HLChu JLim KKim MGfalseLoss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice.<h4>Background</h4>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, leading to progressive paralysis. Both genetic alterations and epigenetic modifications contribute to neuronal dysfunction in the pathogenesis of ALS. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear.<h4>Methods</h4>Convolutional neural network was used to identify an ALS-associated SNP located in the intronic region of MEF2C (rs304152), residing in a putative enhancer element. To examine the alteration of MEF2C transcription by the SNP, we generated HEK293T cells carrying the major or minor allele by CRISPR-Cas9. To verify the role of MEF2C-knockdow2025-01-01T00:00:00Z2025 Feb2026-06-02T00:13:30.356Z2025-04-04T13:11:10.636ZS-EPMC118068873992077510.1186/s13024-024-00792-y