药物靶向调控ID4基因表达的生物信息学预测与分析  

Bioinformatics Scan Analysis for Predicting Drug Targeted Modulation on ID4 Gene Expression

作　　者：卢学春[1] 迟小华[2] 楼方定[3] 朱宏丽[1] 范辉[1] 李素霞[1] 于力[3] 

机构地区：[1]解放军总医院南楼血液科,北京10085 [2]解放军第262医院药剂科,北京100800 [3]解放军总医院血液科,北京100853

出　　处：《中国实验血液学杂志》2007年第3期594-598,共5页Journal of Experimental Hematology

基　　金：国家973重点基金资助项目(编号2005CB522400);国家自然科学基金资助项目(编号39970318);军队"十一五"科技攻关项目

摘　　要：ID4基因低表达与肿瘤发生关系密切,其高表达具有明确的抗白血病作用,但在白血病细胞无表达。本研究初步通过生物信息学方法分析ID4基因启动子的结构,预测调控ID4基因表达的顺式元件及相关药物,为筛选有靶向调控ID4基因表达的药物创造前提。以人类基因组数据库和计算机互联网为平台,钓取ID4基因5′侧翼区3000bp非编码DNA序列和mRNA序列中的ORF序列;利用TESS和Genomax等在线启动子分析软件在人类转录因子数据库中搜索可能存在的顺式结构;利用SAGE和GEO数据库对影响ID4基因表达的相关因素进行分析。结果表明:ID4基因具有II型启动子,在5'-非翻译区的-45bp处有1个典型的TATA盒。在长度为1300bp的ID4启动子区,存在多个顺式结构,其中包括Sp1、c-Myb、abaA、C/EBPalpha、GR、ERE和Zeste可能具有正向调控作用;CCAAT-bindingfactor、GCF、WT1-KTS、HiNF-C和EGR2可能具有负向调控作用。结论:ID4基因的表达可能受糖皮质激素、雌激素、甲状腺素和卵泡刺激素等多种活性物质的调控。Low expression of ID4 gene is tightly related with carcinogenesis and high expression shows a definite anti-leukemia effect, though little expression in some leukemia cells. The main purpose of this preliminary work was to analyze the construction of ID4 gene promoter and to predict the cis elements in the ID4 promoter region by scanning the drug candidate with bioinformatics method. All these work arc the primary part for finding effective drugs in the treatment of leukemia via the way of ID4 expression regulation. According to the data in GenBank and Internet platform, the 5 ：untranslated sequence just upstream of ID40RF was virtually cloned. TESS, Gcnomatix and GenBank databank were used to analyze the cis dements in this area. RSA was used to find the distribution patterns for all these possible elements. SAGE and GEO datasets were used to find active substances which have the effect on the ID4 expression. The rsults indicated that ID4 had a type Ⅱ promoter with a typical TATA box-45 bp upstream the transcriptional original site. There were a lot of various cis elements in the 5 ＇-untranslated region upstream, including both positive clement candidates such as Spl, c-Myb, abaA, GR, ER, Zeste and C/EBPalpha and negative clement candidates such as CCAAT-binding factor, GCF, WT1 -KTS, HiNF-C and EGR2. It is concluded that estrogen, dexamethasone, thyroid hormone and follicle stimulating hormone may participate in the regulation of ID4 gene expression in both positive and negative manners.

关 键 词：ID4基因 白血病 地塞米松 雌激素 卵泡刺激素 生物信息学分析 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]