Nucleophosmin/B23 regulates PCNA promoter through YY1.
Ectopic over-expression of nucleophosmin/B23 caused a marked up-regulation in the amounts of Yin Yang 1 (YY1) and proliferating cellular nuclear antigen (PCNA) proteins. Transfection with nucleophosmin/B23-targeting siRNA induced a decrease in the intracellular amounts of nucleophosmin/B23, YY1, and PCNA. PCNA expression and its promoter activity were attenuated either by nucleophosmin/B23-siRNA or YY1-siRNA. The ChIP assay showed that positive regulation of PCNA is achieved by binding of YY1 to the initiation site of PCNA promoter. The binding of YY1 to the PCNA promoter and histone H4 acetylation was significantly decreased in nucleophosmin/B23-siRNA-treated cells as compared to control vector-transfected cells. Mutation in YY1 binding site resulted in the loss of PCNA promoter activity and the binding of YY1 to the promoter. The results have indicated that YY1 binds to the initiation site of the PCNA promoter along with histone H4 acetylation, leading to transcriptional activity. We have demonstrated that nucleophosmin/B23 plays an important role in the regulation of PCNA through YY1.
Weng
Jing J
JJ
Cancer Biochemistry Laboratory, Department of Pharmacology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-San, Tao-Yuan 333, Taiwan, ROC.
Yung
Benjamin Y M
BY
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D006801:Humans; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000502:physiology*; D000090243:Nucleophosmin; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors / Q000502:physiology*; D050986:YY1 Transcription Factor
D017931:DNA Primers; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C494700:Yy1 protein, rat; D000090243:Nucleophosmin