ArticleProceedings of the National Academy of Sciences of the United States of America2012
Transcription from the second heavy-strand promoter of human mtDNA is repressed by transcription factor A in vitro.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 71 citations in OpenAlex.
- Structural basis for promoter recognition and transcription factor binding and release in human mitochondria.Molecular cell · 2025Article
- Mechanisms and regulation of human mitochondrial transcription.Nature reviews. Molecular cell biology · 2024Review
- Two mitochondrial HMG-box proteins, Cim1 and Abf2, antagonistically regulate mtDNA copy number in Saccharomyces cerevisiae.Nucleic acids research · 2023Article
- Effects of Redox Homeostasis and Mitochondrial Damage on Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2023Review
- 35 Years of TFAM Research: Old Protein, New Puzzles.Biology · 2023Review
- Targeting Mitochondrial DNA Transcription by POLRMT Inhibition or Depletion as a Potential Strategy for Cancer Treatment.Biomedicines · 2023Review
- The human mitochondrial genome contains a second light strand promoter.Molecular cell · 2022Article
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- Mitochondrial and metabolic dysfunction in ageing and age-related diseases.Nature reviews. Endocrinology · 2022Review
- A minimal motif for sequence recognition by mitochondrial transcription factor A (TFAM).Nucleic acids research · 2022Article
- Dynamic features of human mitochondrial DNA maintenance and transcription.Frontiers in cell and developmental biology · 2022Review
- Structure, mechanism, and regulation of mitochondrial DNA transcription initiation.The Journal of biological chemistry · 2020Review
- Functional conservation of mitochondrial RNA levels despite divergent mtDNA organization.BMC research notes · 2020Article
- Mechanisms of mammalian mitochondrial transcription.Protein science : a publication of the Protein Society · 2019Review
- Differences in Liver TFAM Binding to mtDNA and mtDNA Damage between Aged and Extremely Aged Rats.International journal of molecular sciences · 2019Article
- Cytosine methylation of mitochondrial DNA at CpG sequences impacts transcription factor A DNA binding and transcription.Biochimica et biophysica acta. Gene regulatory mechanisms · 2019Article
- Mitochondrial miRNA Determines Chemoresistance by Reprogramming Metabolism and Regulating Mitochondrial Transcription.Cancer research · 2019Article
- Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A.Frontiers in genetics · 2019Review
- Nuclear genes involved in mitochondrial diseases caused by instability of mitochondrial DNA.Journal of applied genetics · 2018Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cell-based studies support the existence of two promoters on the heavy strand of mtDNA: heavy-strand promoter 1 (HSP1) and HSP2. However, transcription from HSP2 has been reported only once in a cell-free system, and never when recombinant proteins have been used. Here, we document transcription from HSP2 using an in vitro system of defined composition. An oligonucleotide template representing positions 596-685 of mtDNA was sufficient to observe transcription by the human mtRNA polymerase (POLRMT) that was absolutely dependent on mitochondrial transcription factor B2 (TFB2M). POLRMT/TFB2M-dependent transcription was inhibited by concentrations of mitochondrial transcription factor A (TFAM) stoichiometric with the transcription template, a condition that activates transcription from the light-strand promoter (LSP) in vitro. Domains of TFAM required for LSP activation were also required for HSP2 repression, whereas other mtDNA binding proteins failed to alter transcriptional output. Binding sites for TFAM were located on both sides of the start site of transcription from HSP2, suggesting that TFAM binding interferes with POLRMT and/or TFB2M binding. Consistent with a competitive binding model for TFAM repression of HSP2, the impact of TFAM concentration on HSP2 transcription was diminished by elevating the POLRMT and TFB2M concentrations. In the context of our previous studies of LSP and HSP1, it is now clear that three promoters exist in human mtDNA. Each promoter has a unique requirement for and/or response to the level of TFAM present, thus implying far greater complexity in the regulation of mammalian mitochondrial transcription than recognized to date.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.