ArticleGenome biology and evolution2014
Transcription factors bind negatively selected sites within human mtDNA genes.
Article in Genome biology and evolution, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- MtDNA meta-analysis reveals both phenotype specificity and allele heterogeneity: a model for differential association.Scientific reports · 2017Pooled it
- Hypoxia leads to reduced mito-nuclear gene expression and increased mtDNA transcriptional pausing in human cells.Communications biology · 2026Article
- Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025Review
- Vertebrates show coordinated elevated expression of mitochondrial and nuclear genes after birth.Genome research · 2025Article
- An updated compendium and reevaluation of the evidence for nuclear transcription factor occupancy over the mitochondrial genome.PloS one · 2025Article
- Mitochondrial replication's role in vertebrate mtDNA strand asymmetry.Open biology · 2023Article
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- The metazoan landscape of mitochondrial DNA gene order and content is shaped by selection and affects mitochondrial transcription.Communications biology · 2023Article
- Human mitochondrial RNA modifications associate with tissue-specific changes in gene expression, and are affected by sunlight and UV exposure.European journal of human genetics : EJHG · 2022Article
- Could Amyloid-β 1-42 or α-Synuclein Interact Directly with Mitochondrial DNA? A Hypothesis.ACS chemical neuroscience · 2022Review
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- Cell Stress Induces Mislocalization of Transcription Factors with Mitochondrial Enrichment.International journal of molecular sciences · 2021Article
- Mitochondrial nucleoid in cardiac homeostasis: bidirectional signaling of mitochondria and nucleus in cardiac diseases.Basic research in cardiology · 2021Review
- Mitonuclear Interactions in the Maintenance of Mitochondrial Integrity.Life (Basel, Switzerland) · 2020Review
- Transposable elements, circular RNAs and mitochondrial transcription in age-related genomic regulation.Development (Cambridge, England) · 2020Review
- Mapping and editing animal mitochondrial genomes: can we overcome the challenges?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Review
- MOTS-c: A Mitochondrial-Encoded Regulator of the Nucleus.BioEssays : news and reviews in molecular, cellular and developmental biology · 2019Review
- Mechanisms of mammalian mitochondrial transcription.Protein science : a publication of the Protein Society · 2019Review
- mtDNA Chromatin-like Organization Is Gradually Established during Mammalian Embryogenesis.iScience · 2019Article
- What Is Nuclear Factor Kappa B (NF-κB) Doing in and to the Mitochondrion?Frontiers in cell and developmental biology · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription of mitochondrial DNA (mtDNA)-encoded genes is thought to be regulated by a handful of dedicated transcription factors (TFs), suggesting that mtDNA genes are separately regulated from the nucleus. However, several TFs, with known nuclear activities, were found to bind mtDNA and regulate mitochondrial transcription. Additionally, mtDNA transcriptional regulatory elements, which were proved important in vitro, were harbored by a deletion that normally segregated among healthy individuals. Hence, mtDNA transcriptional regulation is more complex than once thought. Here, by analyzing ENCODE chromatin immunoprecipitation sequencing (ChIP-seq) data, we identified strong binding sites of three bona fide nuclear TFs (c-Jun, Jun-D, and CEBPb) within human mtDNA protein-coding genes. We validated the binding of two TFs by ChIP-quantitative polymerase chain reaction (c-Jun and Jun-D) and showed their mitochondrial localization by electron microscopy and subcellular fractionation. As a step toward investigating the functionality of these TF-binding sites (TFBS), we assessed signatures of selection. By analyzing 9,868 human mtDNA sequences encompassing all major global populations, we recorded genetic variants in tips and nodes of mtDNA phylogeny within the TFBS. We next calculated the effects of variants on binding motif prediction scores. Finally, the mtDNA variation pattern in predicted TFBS, occurring within ChIP-seq negative-binding sites, was compared with ChIP-seq positive-TFBS (CPR). Motifs within CPRs of c-Jun, Jun-D, and CEBPb harbored either only tip variants or their nodal variants retained high motif prediction scores. This reflects negative selection within mtDNA CPRs, thus supporting their functionality. Hence, human mtDNA-coding sequences may have dual roles, namely coding for genes yet possibly also possessing regulatory potential.
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