title: Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression.
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 regulatingSETgene 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.
authors: 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.|Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. xu_s@mercer.edu.
authors: Siliang
authors: S
authors: Xu
authors: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China. cuiygnj@njmu.edu.cn.
authors: Ping
authors: P
authors: Duan
authors: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. li_j@mercer.edu.
authors: Jinping
authors: J
authors: Li
authors: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. senkowskitristan@savcds.org.
authors: Tristan
authors: T
authors: Senkowski
authors: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. guo_f@mercer.edu.|Department of Histology and Embryology, Shantou University Medical College, Shantou 515000, China. guo_f@mercer.edu.
authors: Fengbiao
authors: F
authors: Guo
authors: Department of Histology and Embryology, Shantou University Medical College, Shantou 515000, China. chenhb@stu.edu.cn.
authors: Haibin
authors: H
authors: Chen
authors: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. romero_ah@med.mercer.edu.
authors: Alberto
authors: A
authors: Romero
authors: 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.
authors: Yugui
authors: Y
authors: Cui
authors: 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.
authors: Jiayin
authors: J
authors: Liu
authors: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA. jiang_s@mercer.edu.|Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China. jiang_s@mercer.edu.
authors: Shi-Wen
authors: SW
authors: Jiang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D056488:Histone Chaperones / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; C513473:SET protein, human; D014157:Transcription Factors; C062076:zinc finger protein, X-linked
keywords: I2PP2A (protein phosphatase 2A inhibitor); SET (SE Translocation); ZFX (Zinc finger and X-linked transcription factor); gynecologic cancers; transcriptional regulation