GSE162384
Mitochondrial transcription factor A (TFAM) represses the expression of interferon signaling genes in human lung epithelial cells
Mitochondrial transcription factor A (TFAM) is associated with a number of neurodegenerative diseases and also with asthma. TFAM deficiency-induced mitochondrial DNA stress primes the antiviral innate immune response in mouse embryonic fibroblasts. In this study, we overexpressed TFAM in human lung epithelial cells (A549), then obtained and analyzed the TFAM-regulated transcriptome by Illumina-sequencing technology. We found that TFAM overexpression down-regulated and up-regulated the expression 642 and 169 genes (DEGs), respectively. The TFAM-repressed genes were highly enriched in cytokine-mediated signaling pathway, type I interferon- and INF??mediated signaling pathways, and viral response pathways. We also revealed that 2563 alternative splicing events in 1796 genes (ASG) were de-regulated upon TFAM overexpression. These TFAM-responding ASGs were strongly enriched in DNA repair, nerve growth factor receptor signaling pathway, and also transcription regulation. Further analysis revealed that the promoters of TFAM-repressed DEGs were enriched by DNA binding motifs of transcription factors whose alternative splicing regulated by TFAM. These findings suggested that TFAM regulates not only immune response gene expression in human lung epithelial cells, but also alternative splicing which may play a role in mediating transcriptional regulation. This TFAM-centered gene regulation network could be targeted in developing therapies against various diseases. Overall design: Detecting the expression level of differential genes and alternative splicing after TFAM overexpression in A549 cells by RNA-seq