PML通过转录调控CTCF影响C-Myc表达的机制研究

PML Represses C-Myc Expression through Transcriptional Regulation of CTCF

该研究探讨了PML(promyelocytic leukemia protein)对多功能转录因子CTCF(CCCTCbinding factor)的转录调控及其下游靶基因C-Myc的功能影响。通过荧光定量PCR方法分析儿童急性淋巴细胞白血病样本中PML和CTCF基因的表达水平,并分析二者之间的相关性。构建了PML与CTCF真核表达载体,在共转染细胞中,利用荧光定量PCR方法和Western blot分析PML对CTCF表达水平的影响。通过双荧光素报告基因系统分析了PML对CTCF启动子区的调控,并研究了其对CTCF下游靶基因C-Myc的表达水平的影响。结果显示,在临床样本中PML与CTCF表达水平存在负相关性,PML通过抑制CTCF的转录降低CTCF的表达水平,干扰CTCF对下游靶基因C-Myc的调控功能。同时,在CTCF的启动子区域可能存在着PML的结合区域,从而导致CTCF的启动子活性被抑制。

This study investigated the effect of promyelocytic leukemia protein(PML) on transcription regulation of CCCTC-binding factor(CTCF) and its downstream target gene C-Myc. The expression levels of PML and CTCF in clinical samples were analyzed by using fluorescence quantitative PCR, and the correlation between them was also analyzed. PML and CTCF eukaryotic expression vectors were constructed, and the effect of PML on CTCF expression level was analyzed by fluorescence quantitative PCR and Western blot in co-transfected cells. The regulation of PML on CTCF promoter region was analyzed through the Dual-Luciferase reporter gene system, and the influence of PML on the expression level of C-Myc downstream target gene of CTCF. It showed that there was a negative correlation between the expression of PML and CTCF in children ALL. PML reduced the expression of CTCF by inhibiting the transcription of CTCF and interfered with the regulation of the CTCF downstream target gene C-Myc. At the same time, there may be a binding region of PML in the promoter region of CTCF, resulting in inhibition of CTCF promoter activity.