Mitochondrial DNA copy number reduction via in vitro TFAM knockout remodels the nuclear epigenome and transcriptome.

ABSTRACT: Mitochondrial DNA copy number (mtDNA-CN) is associated with several age-related chronic diseases and is a predictor of all-cause mortality. Here, we examine site-specific differential nuclear DNA (nDNA) methylation and differential gene expression resulting from in vitro reduction of mtDNA-CN to uncover shared genes and biological pathways mediating the effect of mtDNA-CN on disease. Epigenome and transcriptome profiles were generated for three independent human embryonic kidney (HEK293T) cell lines harbouring a mitochondrial transcription factor A (TFAM) heterozygous knockout generated via CRISPR-Cas9, and matched control lines. We identified 4,242 differentially methylated sites, 228 differentially methylated regions, and 179 differentially expressed genes associated with m

SUBMITTER: Nguyen J 

PROVIDER: S-EPMC10862824 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature