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The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model

Functional short tandem repeats (STR) are polymorphic in the population, and the number of repeats regulates the expression of nearby genes (known as expression STR, eSTR). STR in IGF1 promoter has been extensively studied for its association with IGF1 concentration in blood and various clinical tra...

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Autores principales: Chen, Holly Y., Ma, Suk Ling, Huang, Wei, Ji, Lindan, Leung, Vincent H. K., Jiang, Honglin, Yao, Xiaoqiang, Tang, Nelson L. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133613/
https://www.ncbi.nlm.nih.gov/pubmed/27910883
http://dx.doi.org/10.1038/srep38225
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author Chen, Holly Y.
Ma, Suk Ling
Huang, Wei
Ji, Lindan
Leung, Vincent H. K.
Jiang, Honglin
Yao, Xiaoqiang
Tang, Nelson L. S.
author_facet Chen, Holly Y.
Ma, Suk Ling
Huang, Wei
Ji, Lindan
Leung, Vincent H. K.
Jiang, Honglin
Yao, Xiaoqiang
Tang, Nelson L. S.
author_sort Chen, Holly Y.
collection PubMed
description Functional short tandem repeats (STR) are polymorphic in the population, and the number of repeats regulates the expression of nearby genes (known as expression STR, eSTR). STR in IGF1 promoter has been extensively studied for its association with IGF1 concentration in blood and various clinical traits and represents an important eSTR. We previously used an in-vitro luciferase reporter model to examine the interaction between STRs and SNPs in IGF1 promoter. Here, we further explored the mechanism how the number of repeats of the STR regulates gene transcription. An inverse correlation between the number of repeats and the extent of transactivation was found in a haplotype consisting of three promoter SNPs (C-STR-T-T). We showed that these adjacent SNPs located outside the STR were required for the STR to function as eSTR. The C allele of rs35767 provides a binding site for CCAAT/enhancer-binding-protein δ (C/EBPD), which is essential for the gradational transactivation property of eSTR and FOXA3 may also be involved. Therefore, we propose a mechanism in which the gradational transactivation by the eSTR is caused by the interaction of one or more transcriptional complexes located outside the STR, rather than by direct binding to a repeat motif of the STR.
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spelling pubmed-51336132017-01-27 The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model Chen, Holly Y. Ma, Suk Ling Huang, Wei Ji, Lindan Leung, Vincent H. K. Jiang, Honglin Yao, Xiaoqiang Tang, Nelson L. S. Sci Rep Article Functional short tandem repeats (STR) are polymorphic in the population, and the number of repeats regulates the expression of nearby genes (known as expression STR, eSTR). STR in IGF1 promoter has been extensively studied for its association with IGF1 concentration in blood and various clinical traits and represents an important eSTR. We previously used an in-vitro luciferase reporter model to examine the interaction between STRs and SNPs in IGF1 promoter. Here, we further explored the mechanism how the number of repeats of the STR regulates gene transcription. An inverse correlation between the number of repeats and the extent of transactivation was found in a haplotype consisting of three promoter SNPs (C-STR-T-T). We showed that these adjacent SNPs located outside the STR were required for the STR to function as eSTR. The C allele of rs35767 provides a binding site for CCAAT/enhancer-binding-protein δ (C/EBPD), which is essential for the gradational transactivation property of eSTR and FOXA3 may also be involved. Therefore, we propose a mechanism in which the gradational transactivation by the eSTR is caused by the interaction of one or more transcriptional complexes located outside the STR, rather than by direct binding to a repeat motif of the STR. Nature Publishing Group 2016-12-02 /pmc/articles/PMC5133613/ /pubmed/27910883 http://dx.doi.org/10.1038/srep38225 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chen, Holly Y.
Ma, Suk Ling
Huang, Wei
Ji, Lindan
Leung, Vincent H. K.
Jiang, Honglin
Yao, Xiaoqiang
Tang, Nelson L. S.
The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model
title The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model
title_full The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model
title_fullStr The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model
title_full_unstemmed The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model
title_short The mechanism of transactivation regulation due to polymorphic short tandem repeats (STRs) using IGF1 promoter as a model
title_sort mechanism of transactivation regulation due to polymorphic short tandem repeats (strs) using igf1 promoter as a model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133613/
https://www.ncbi.nlm.nih.gov/pubmed/27910883
http://dx.doi.org/10.1038/srep38225
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