Abstract
Mitochondria contain a 16.6 kb circular genome encoding 13 proteins as well as mitochondrial tRNAs and rRNAs. Copies of the genome are organized into nucleoids containing both DNA and proteins, including the machinery required for mtDNA replication and transcription. The transcription factor TFAM is critical for initiation of transcription and replication of the genome, and is also thought to perform a packaging function. Although specific binding sites required for initiation of transcription have been identified in the D-loop, little is known about the characteristics of TFAM binding in its nonspecific packaging state. In addition, it is unclear whether TFAM also plays a role in the regulation of nuclear gene expression. Here we investigate these questions by using ChIP-seq to directly localize TFAM binding to DNA in human cells. Our results demonstrate that TFAM uniformly coats the whole mitochondrial genome, with no evidence of robust TFAM binding to the nuclear genome. Our study represents the first high-resolution assessment of TFAM binding on a genome-wide scale in human cells.
Highlights
Mitochondria are essential eukaryotic organelles, serving as the epicenter of ATP production in the cell through oxidative phosphorylation
To characterize TFAM binding to Mitochondrial DNA (mtDNA), we examined the forward and reverse strand read distribution after mapping TFAM ChIP-seq and input library reads to the mitochondrial genome
Previous in vitro studies have suggested that TFAM binds to light strand promoter (LSP) and heavy strand promoter 1 (HSP1), and that it may bind nonspecifically in a phased manner
Summary
Mitochondria are essential eukaryotic organelles, serving as the epicenter of ATP production in the cell through oxidative phosphorylation To perform this bioenergetic function, mitochondria utilize gene products encoded by the mitochondrial genome, a circular DNA that is 16.6 kb long. Mitochondrial DNA (mtDNA) encodes thirteen components of the electron transport chain, as well as 22 tRNAs and two ribosomal RNA genes These gene products are essential for the proper function of the respiratory chain, and maintenance of mtDNA levels and sequence fidelity is essential for cellular bioenergetics. Increasing mtDNA copy number promotes cell survival or function in many models of disease associated with decreased mtDNA abundance, such as diabetes [12,17], aging [18], Alzheimer’s [19], and Parkinson’s [20,21]. It is critical to understand how mtDNA copy number and integrity are maintained
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
