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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...

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Autores principales: Malarkey, Christopher S., Bestwick, Megan, Kuhlwilm, Jane E., Shadel, Gerald S., Churchill, Mair E. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2012
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.
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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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