两种组蛋白乙酰转移酶P/CAF和p300协同提高WT1基因启动子和内部增强子活性

Histone Acetyltransferase P/CAF and p300 Synergically Increases the Promoter and Intronic Enhancer Activity of WT1 Gene

目的P/CAF(p300/CBP-associated factor)和p300都是组蛋白乙酰转移酶家族成员,它们都含有组蛋白乙酰转移酶(histone acetyltransferase,HAT)区。本文的目的是检测P/CAF和p300及其HAT区在维耳姆斯氏瘤1(WT1)基因转录调控中的作用。方法构建WT1启动子/内部增强子/荧光素酶报告基因质粒,通过瞬时转染和荧光素酶活性测定实验检测P/CAF和p300及其HAT区在WT1基因转录调控中的作用。结果P/CAF和p300都能提高WT1基因启动子和内部增强子活性。当P/CAF和p300共同作用时,它们能协同提高WT1基因的转录活性。在WT1基因转录激活的过程中,P/CAF和p300的HAT区发挥重要作用。结论P/CAF和p300能够协同提高WT1基因的转录活性,在此过程中,P/CAF和p300的HAT区发挥重要作用。

Objective P/CAF（p300/CBP-associated factor） and p300 are both members of histone acetyltransferase family, each of them contains a histone acetyhransferase （HAT） domain. The object of this essay is to examine the roles of P/CAF, p300 and their HAT domains on Wilms＇ tumor 1（WT1）gene transcriptional regulation. Methods WT1 promoter/intronic enhancer/luciferase reporter gene plasmid was constructed, then the roles of P/CAF, p300 and their HAT domains on WT1 gene transcriptional regulation were determined by transient transfection and luciferase acitivity assays. Results P/CAF and p300 each increased the promoter and intronic enhancer acitivity of WT1 gene. P/CAF and p300 synergically increased the transcriptional activity of WT1 gene when they acted combinatorially. The HAT domains of P/CAF and p300 were important in the transcriptional activation of WT1 gene. Conclusion P/CAF and p300 synergically increase the transcriptional activity of WT1 gene, their HAT domains are important in the course of WT1 gene transcriptional activation.