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Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA
Mitochondrial transcription factor A (mtTFA/TFAM) is a nucleus-encoded, high-mobility-group-box (HMG-box) protein that regulates transcription of the mitochondrial genome by specifically recognizing light-strand and heavy-strand promoters (LSP, HSP1). TFAM also binds mitochondrial DNA in a non-seque...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258160/ https://www.ncbi.nlm.nih.gov/pubmed/21948790 http://dx.doi.org/10.1093/nar/gkr787 |
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author | Malarkey, Christopher S. Bestwick, Megan Kuhlwilm, Jane E. Shadel, Gerald S. Churchill, Mair E. A. |
author_facet | Malarkey, Christopher S. Bestwick, Megan Kuhlwilm, Jane E. Shadel, Gerald S. Churchill, Mair E. A. |
author_sort | Malarkey, Christopher S. |
collection | PubMed |
description | Mitochondrial transcription factor A (mtTFA/TFAM) is a nucleus-encoded, high-mobility-group-box (HMG-box) protein that regulates transcription of the mitochondrial genome by specifically recognizing light-strand and heavy-strand promoters (LSP, HSP1). TFAM also binds mitochondrial DNA in a non-sequence specific (NSS) fashion and facilitates its packaging into nucleoid structures. However, the requirement and contribution of DNA-bending for these two different binding modes has not been addressed in detail, which prompted this comparison of binding and bending properties of TFAM on promoter and non-promoter DNA. Promoter DNA increased the stability of TFAM to a greater degree than non-promoter DNA. However, the thermodynamic properties of DNA binding for TFAM with promoter and non-specific (NS) DNA were similar to each other and to other NSS HMG-box proteins. Fluorescence resonance energy transfer assays showed that TFAM bends promoter DNA to a greater degree than NS DNA. In contrast, TFAM lacking the C-terminal tail distorted both promoter and non-promoter DNA to a significantly reduced degree, corresponding with markedly decreased transcriptional activation capacity at LSP and HSP1 in vitro. Thus, the enhanced bending of promoter DNA imparted by the C-terminal tail is a critical component of the ability of TFAM to activate promoter-specific initiation by the core mitochondrial transcription machinery. |
format | Online Article Text |
id | pubmed-3258160 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32581602012-01-17 Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA Malarkey, Christopher S. Bestwick, Megan Kuhlwilm, Jane E. Shadel, Gerald S. Churchill, Mair E. A. Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics Mitochondrial transcription factor A (mtTFA/TFAM) is a nucleus-encoded, high-mobility-group-box (HMG-box) protein that regulates transcription of the mitochondrial genome by specifically recognizing light-strand and heavy-strand promoters (LSP, HSP1). TFAM also binds mitochondrial DNA in a non-sequence specific (NSS) fashion and facilitates its packaging into nucleoid structures. However, the requirement and contribution of DNA-bending for these two different binding modes has not been addressed in detail, which prompted this comparison of binding and bending properties of TFAM on promoter and non-promoter DNA. Promoter DNA increased the stability of TFAM to a greater degree than non-promoter DNA. However, the thermodynamic properties of DNA binding for TFAM with promoter and non-specific (NS) DNA were similar to each other and to other NSS HMG-box proteins. Fluorescence resonance energy transfer assays showed that TFAM bends promoter DNA to a greater degree than NS DNA. In contrast, TFAM lacking the C-terminal tail distorted both promoter and non-promoter DNA to a significantly reduced degree, corresponding with markedly decreased transcriptional activation capacity at LSP and HSP1 in vitro. Thus, the enhanced bending of promoter DNA imparted by the C-terminal tail is a critical component of the ability of TFAM to activate promoter-specific initiation by the core mitochondrial transcription machinery. Oxford University Press 2012-01 2011-09-23 /pmc/articles/PMC3258160/ /pubmed/21948790 http://dx.doi.org/10.1093/nar/gkr787 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Gene Regulation, Chromatin and Epigenetics Malarkey, Christopher S. Bestwick, Megan Kuhlwilm, Jane E. Shadel, Gerald S. Churchill, Mair E. A. Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA |
title | Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA |
title_full | Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA |
title_fullStr | Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA |
title_full_unstemmed | Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA |
title_short | Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA |
title_sort | transcriptional activation by mitochondrial transcription factor a involves preferential distortion of promoter dna |
topic | Gene Regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258160/ https://www.ncbi.nlm.nih.gov/pubmed/21948790 http://dx.doi.org/10.1093/nar/gkr787 |
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