Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Siliang Xu
,
Shi-Wen Jiang
* ,
Fengbiao Guo
ORCID logo ,
Tristan Senkowski
,
Jinping Li
,
Haibin Chen
,
Alberto Romero
,
Yugui Cui
,
Jiayin Liu
*
Version 1 : Received: 8 October 2016 / Approved: 8 October 2016 / Online: 8 October 2016 (10:52:00 CEST)

A peer-reviewed article of this Preprint also exists.

Xu, S.; Duan, P.; Li, J.; Senkowski, T.; Guo, F.; Chen, H.; Romero, A.; Cui, Y.; Liu, J.; Jiang, S.-W. Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression. Int. J. Mol. Sci. 2016, 17, 1737. Xu, S.; Duan, P.; Li, J.; Senkowski, T.; Guo, F.; Chen, H.; Romero, A.; Cui, Y.; Liu, J.; Jiang, S.-W. Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression. Int. J. Mol. Sci. 2016, 17, 1737.

Abstract

SET 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 Alzheimer's disease patients, 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 site located 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 site 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.

Keywords

SET; I2PP2A; ZFX; transcriptional regulation; gynecologic cancers

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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