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A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity

The c-myb promoter contains multiple GGA repeats beginning 17 bp downstream of the transcription initiation site. GGA repeats have been previously shown to form unusual DNA structures in solution. Results from chemical footprinting, circular dichroism and RNA and DNA polymerase arrest assays on olig...

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Autores principales: Palumbo, SunMi L., Memmott, Regan M., Uribe, Diana J., Krotova-Khan, Yulia, Hurley, Laurence H., Ebbinghaus, Scot W.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330228/
https://www.ncbi.nlm.nih.gov/pubmed/18252774
http://dx.doi.org/10.1093/nar/gkm1069
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author Palumbo, SunMi L.
Memmott, Regan M.
Uribe, Diana J.
Krotova-Khan, Yulia
Hurley, Laurence H.
Ebbinghaus, Scot W.
author_facet Palumbo, SunMi L.
Memmott, Regan M.
Uribe, Diana J.
Krotova-Khan, Yulia
Hurley, Laurence H.
Ebbinghaus, Scot W.
author_sort Palumbo, SunMi L.
collection PubMed
description The c-myb promoter contains multiple GGA repeats beginning 17 bp downstream of the transcription initiation site. GGA repeats have been previously shown to form unusual DNA structures in solution. Results from chemical footprinting, circular dichroism and RNA and DNA polymerase arrest assays on oligonucleotides representing the GGA repeat region of the c-myb promoter demonstrate that the element is able to form tetrad:heptad:heptad:tetrad (T:H:H:T) G-quadruplex structures by stacking two tetrad:heptad G-quadruplexes formed by two of the three (GGA)(4) repeats. Deletion of one or two (GGA)(4) motifs destabilizes this secondary structure and increases c-myb promoter activity, indicating that the G-quadruplexes formed in the c-myb GGA repeat region may act as a negative regulator of the c-myb promoter. Complete deletion of the c-myb GGA repeat region abolishes c-myb promoter activity, indicating dual roles of the c-myb GGA repeat element as both a transcriptional repressor and an activator. Furthermore, we demonstrated that Myc-associated zinc finger protein (MAZ) represses c-myb promoter activity and binds to the c-myb T:H:H:T G-quadruplexes. Our findings show that the T:H:H:T G-quadruplex-forming region in the c-myb promoter is a critical cis-acting element and may repress c-myb promoter activity through MAZ interaction with G-quadruplexes in the c-myb promoter.
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spelling pubmed-23302282008-05-05 A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity Palumbo, SunMi L. Memmott, Regan M. Uribe, Diana J. Krotova-Khan, Yulia Hurley, Laurence H. Ebbinghaus, Scot W. Nucleic Acids Res Molecular Biology The c-myb promoter contains multiple GGA repeats beginning 17 bp downstream of the transcription initiation site. GGA repeats have been previously shown to form unusual DNA structures in solution. Results from chemical footprinting, circular dichroism and RNA and DNA polymerase arrest assays on oligonucleotides representing the GGA repeat region of the c-myb promoter demonstrate that the element is able to form tetrad:heptad:heptad:tetrad (T:H:H:T) G-quadruplex structures by stacking two tetrad:heptad G-quadruplexes formed by two of the three (GGA)(4) repeats. Deletion of one or two (GGA)(4) motifs destabilizes this secondary structure and increases c-myb promoter activity, indicating that the G-quadruplexes formed in the c-myb GGA repeat region may act as a negative regulator of the c-myb promoter. Complete deletion of the c-myb GGA repeat region abolishes c-myb promoter activity, indicating dual roles of the c-myb GGA repeat element as both a transcriptional repressor and an activator. Furthermore, we demonstrated that Myc-associated zinc finger protein (MAZ) represses c-myb promoter activity and binds to the c-myb T:H:H:T G-quadruplexes. Our findings show that the T:H:H:T G-quadruplex-forming region in the c-myb promoter is a critical cis-acting element and may repress c-myb promoter activity through MAZ interaction with G-quadruplexes in the c-myb promoter. Oxford University Press 2008-04 2008-02-05 /pmc/articles/PMC2330228/ /pubmed/18252774 http://dx.doi.org/10.1093/nar/gkm1069 Text en © 2008 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Molecular Biology
Palumbo, SunMi L.
Memmott, Regan M.
Uribe, Diana J.
Krotova-Khan, Yulia
Hurley, Laurence H.
Ebbinghaus, Scot W.
A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity
title A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity
title_full A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity
title_fullStr A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity
title_full_unstemmed A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity
title_short A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity
title_sort novel g-quadruplex-forming gga repeat region in the c-myb promoter is a critical regulator of promoter activity
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2330228/
https://www.ncbi.nlm.nih.gov/pubmed/18252774
http://dx.doi.org/10.1093/nar/gkm1069
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