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Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression

SET (SE Translocation) protein carries out multiple functions including those for protein phosphatase 2A (PP2A) inhibition, histone modification, DNA repair, and gene regulation. SET overexpression has been detected in brain neurons of patients suffering Alzheimer’s disease, follicle theca cells of...

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Autores principales: Xu, Siliang, Duan, Ping, Li, Jinping, Senkowski, Tristan, Guo, Fengbiao, Chen, Haibin, Romero, Alberto, Cui, Yugui, Liu, Jiayin, Jiang, Shi-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085766/
https://www.ncbi.nlm.nih.gov/pubmed/27775603
http://dx.doi.org/10.3390/ijms17101737
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author Xu, Siliang
Duan, Ping
Li, Jinping
Senkowski, Tristan
Guo, Fengbiao
Chen, Haibin
Romero, Alberto
Cui, Yugui
Liu, Jiayin
Jiang, Shi-Wen
author_facet Xu, Siliang
Duan, Ping
Li, Jinping
Senkowski, Tristan
Guo, Fengbiao
Chen, Haibin
Romero, Alberto
Cui, Yugui
Liu, Jiayin
Jiang, Shi-Wen
author_sort Xu, Siliang
collection PubMed
description SET (SE Translocation) protein carries out multiple functions including those for protein phosphatase 2A (PP2A) inhibition, histone modification, DNA repair, and gene regulation. SET overexpression has been detected in brain neurons of patients suffering Alzheimer’s disease, follicle theca cells of Polycystic Ovary Syndrome (PCOS) patients, and ovarian cancer cells, indicating that SET may play a pathological role for these disorders. SET transcript 2, produced by a specific promoter, represents a major transcript variant in different cell types. In this study, we characterized the transcriptional activation of human SET transcript 2 promoter in HeLa cells. Promoter deletion experiments and co-transfection assays indicated that ZFX, the Zinc finger and X-linked transcription factor, was able to transactivate the SET promoter. A proximal promoter region containing four ZFX-binding sites was found to be critical for the ZFX-mediated transactivation. Mutagenesis study indicated that the ZFX-binding site located the closest to the transcription start site accounted for most of the ZFX-mediated transactivity. Manipulation of ZFX levels by overexpression or siRNA knockdown confirmed the significance and specificity of the ZFX-mediated SET promoter activation. Chromatin immunoprecipitation results verified the binding of ZFX to its cognate sites in the SET promoter. These findings have led to identification of ZFX as an upstream factor regulating SET gene expression. More studies are required to define the in vivo significance of this mechanism, and specifically, its implication for several benign and malignant diseases related to SET dysregulation.
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spelling pubmed-50857662016-11-01 Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression Xu, Siliang Duan, Ping Li, Jinping Senkowski, Tristan Guo, Fengbiao Chen, Haibin Romero, Alberto Cui, Yugui Liu, Jiayin Jiang, Shi-Wen Int J Mol Sci Article SET (SE Translocation) protein carries out multiple functions including those for protein phosphatase 2A (PP2A) inhibition, histone modification, DNA repair, and gene regulation. SET overexpression has been detected in brain neurons of patients suffering Alzheimer’s disease, follicle theca cells of Polycystic Ovary Syndrome (PCOS) patients, and ovarian cancer cells, indicating that SET may play a pathological role for these disorders. SET transcript 2, produced by a specific promoter, represents a major transcript variant in different cell types. In this study, we characterized the transcriptional activation of human SET transcript 2 promoter in HeLa cells. Promoter deletion experiments and co-transfection assays indicated that ZFX, the Zinc finger and X-linked transcription factor, was able to transactivate the SET promoter. A proximal promoter region containing four ZFX-binding sites was found to be critical for the ZFX-mediated transactivation. Mutagenesis study indicated that the ZFX-binding site located the closest to the transcription start site accounted for most of the ZFX-mediated transactivity. Manipulation of ZFX levels by overexpression or siRNA knockdown confirmed the significance and specificity of the ZFX-mediated SET promoter activation. Chromatin immunoprecipitation results verified the binding of ZFX to its cognate sites in the SET promoter. These findings have led to identification of ZFX as an upstream factor regulating SET gene expression. More studies are required to define the in vivo significance of this mechanism, and specifically, its implication for several benign and malignant diseases related to SET dysregulation. MDPI 2016-10-20 /pmc/articles/PMC5085766/ /pubmed/27775603 http://dx.doi.org/10.3390/ijms17101737 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Siliang
Duan, Ping
Li, Jinping
Senkowski, Tristan
Guo, Fengbiao
Chen, Haibin
Romero, Alberto
Cui, Yugui
Liu, Jiayin
Jiang, Shi-Wen
Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression
title Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression
title_full Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression
title_fullStr Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression
title_full_unstemmed Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression
title_short Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression
title_sort zinc finger and x-linked factor (zfx) binds to human set transcript 2 promoter and transactivates set expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085766/
https://www.ncbi.nlm.nih.gov/pubmed/27775603
http://dx.doi.org/10.3390/ijms17101737
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