Analysis of Epigenetic Modification in Leber's Hereditary Optic Neuropathy (LHON) Cells

Leber's Hereditary Optic Neuropathy (LHON) is a mitochondrially inherited vision loss disease due to pathogenic mitochondrial mutations in complex 1 encoding genes which are incurable to date. Mitochondrial respiratory chain complex 1 consists of 45 subunits and NDUFS4 is a nuclear-encoded accessory submit which has a significant role in mitochondrial complex 1 assembly. This preliminary study focuses on the histone modification changes in the NDUFS4 gene. For this study chromatin immunoprecipitation (ChIP) assay was performed using LHON ND4 mutant cell lines and PBMC from a healthy control. Five histone modification antibodies such as H3K18Ac, H3K27Ac, H3K9Me2, H3K4Me3, and H3K27Me3 were used for the experiment. ChIP-qPCR was performed to determine the histone enrichment in the NDUFS4 promoter region. ChIP-qPCR data showed that H3K18Ac histone enrichment has variation in LHON ND4 mutant cells compared to PBMCs. As a primary step, this study has tried to figure out the histone modification changes in the NDUFS4 gene in the LHON cells derived from ND4 mutant patients and control PBMCs. Epigenetic studies in nuclear-encoded mitochondrial proteins in LHON may help researchers for a better understanding of disease pathology.