Cloning and characterization of the BRD7 gene promoter
Cloning and characterization of the BRD7 gene promoter
复制标题
DOI：
10.1089/dna.2006.25.346
复制
发表时间：
2006-06-01
影响因子：
3.1
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
--
作者：
Liu, Huaying;Peng, Cong;Li, Guiyuan
BRD 7是一个新的布罗莫结构域基因，编码一种蛋白，通过转录调控一些细胞周期相关基因来抑制细胞生长和细胞周期进程。它的转录表达下调已被证明是至关重要的鼻咽癌（NPC）的发病机制。关于控制BRD 7基因表达的转录机制知之甚少。在本文中，我们已经确定了BRD 7基因的5'调控区，以了解其表达调控的分子机制。瞬时转染的结果表明，分析的BRD 7基因的上游序列可能包含一些重要的，但不足够的序列信息，赋予BRD 7基因表达的细胞类型特异性。进一步的分析表明，一系列的缺失，一个125 bp的区域所需的BRD 7基因的基础启动子活性。来自ChIP和EMSA的结果表明该启动子对Sp1、E2 F和E2 F6有响应。所有这些都表明转录因子Sp1、E2 F和E2 F-6在BRD 7启动子区域中相关并调节BRD 7启动子活性的可能机制。总之，这些结果将有助于更好地理解BRD 7基因在信号依赖性转录调控中的作用，并开发新的试剂用于治疗NPC中BRD 7基因的上调。
BRD7, a novel bromodomain gene, encodes a protein that inhibits cell growth and cell cycle progression by transcriptional regulation of some cell cycle-related genes. Its transcriptional down-expression has been shown to be critical to the pathogenesis of Nasopharyngeal carcinoma ( NPC). Little is known about the transcriptional mechanisms controlling BRD7 gene expression. In this paper, we have characterized the 5' regulatory region of the BRD7 gene in order to understand the molecular mechanisms regulating its expression. Transient transfection results suggested that the analyzed upstream sequences of the BRD7 gene might contain some important but not sufficient sequence information to confer the cell-type specificity of BRD7 gene expression. Further analysis with a series of deletions demonstrated that a 125-bp region was required for the basal promoter activity of the BRD7 gene. Results from ChIP and EMSA indicated that the promoter was responsive to Sp1, E2F, and E2F6. All of these suggest a possible mechanism that transcriptional factor Sp1, E2F, and E2F-6 are associated in the BRD7 promoter region and regulate BRD7 promoter activity. Taken together, these results will help to better understand the role of the BRD7 gene in signal-dependent transcriptional regulation, and to develop new reagents for therapeutic upregulation of the BRD7 gene in NPC.