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Int J Mol Sci. 2016 Oct 20;17(10). pii: E1737.

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

Author information

1
The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. xu_s@mercer.edu.
2
Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. xu_s@mercer.edu.
3
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China. cuiygnj@njmu.edu.cn.
4
Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. li_j@mercer.edu.
5
Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. senkowskitristan@savcds.org.
6
Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. guo_f@mercer.edu.
7
Department of Histology and Embryology, Shantou University Medical College, Shantou 515000, China. guo_f@mercer.edu.
8
Department of Histology and Embryology, Shantou University Medical College, Shantou 515000, China. chenhb@stu.edu.cn.
9
Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. romero_ah@med.mercer.edu.
10
The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. cuiygnj@njmu.edu.cn.
11
The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. jyliu_nj@njmu.edu.cn.
12
Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. jiang_s@mercer.edu.
13
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China. jiang_s@mercer.edu.

Abstract

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.

KEYWORDS:

I2PP2A (protein phosphatase 2A inhibitor); SET (SE Translocation); ZFX (Zinc finger and X-linked transcription factor); gynecologic cancers; transcriptional regulation

PMID:
27775603
PMCID:
PMC5085766
DOI:
10.3390/ijms17101737
[Indexed for MEDLINE]
Free PMC Article

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