Molecular mechanism for general regulation on transcription

转录一般调控的分子机制

• 批准号: 09480184
• 负责人: TAMURA Taka-aki
• 金额: $ 4.61万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09480184/
• 关键词: TBP; TATA-box; transcription; TIP; TIP; 転写因子; 転因制御

We previously identified a novel TBP-interacting protein (TIP 120 from rat liver. In this study, we demonstrated that recombinant TIP 120 activated the basal level of transcription from various kinds of promoters regardless of the template DNA topology and the presence of TFIIE/TFIIH and TAFs. Kinetic studies suggested that TIP 120 functioned during preinitiation complex formation at the step of RNAP II/TFIIF recruitment to the promoter, but not after the completion of preinitiation complex (PIG) formation. EMSA showed that TIP 120 enhanced PIG formation by overcoming a kinetic impediment to RNAP II/TFIIF integration into the TBP/TFIIB- DNA-complex. Deletion analysis demonstrated that the N-terminal 412 residues including an acidic region and the TBP-binding domain is required for TIP120 function. Interestingly, TIP 120 also stimulated RNAP I- and Ill-driven transcription in vitro. In mouse cells, ectopically expressed TIP 120 enhanced transcription from all three classes (class I, II, and III) of promoters. The TIP 120 nuclear staining patterns changed from sharp foci to large speckles upon retinoic acid treatment. Moreover, some TIP 120 regions in HEp-2 cells were colocalized with the PML oncogenic domains.

我们先前从大鼠肝脏中鉴定了一种新的TBP相互作用蛋白（TIP 120）。在这项研究中，我们证明了重组TIP 120激活了各种启动子的基础水平的转录，而不管模板DNA拓扑结构和TFIIE/TFIIH和TAF的存在。动力学研究表明，TIP 120的功能在preinitiation复合物形成的RNAP II/TFIIF招聘到启动子的步骤，但不是完成后preinitiation复合物（PIG）的形成。EMSA显示TIP 120通过克服RNAP II/TFIIF整合到TBP/TFIIB-DNA复合物中的动力学障碍来增强PIG形成。缺失分析表明，包括酸性区域和TBP结合结构域在内的N-末端412个残基是TIP 120功能所必需的。有趣的是，TIP 120还在体外刺激RNAP I和III驱动的转录。在小鼠细胞中，异位表达的TIP 120增强了所有三类（I类、II类和III类）启动子的转录。TIP 120核染色模式在视黄酸处理后从尖锐病灶变为大斑点。此外，HEp-2细胞中的一些TIP 120区域与PML致癌结构域共定位。

项目成果

T.Ohbayashi, Y.Makino, & T.Tamura: "Identification of a mouse TBP-like protein(TLP)distantly related to the Drosophila TBP-related factor." N.A.R.27. 750-755 (1999)

T.Ohbayashi，Y.Makino，

大林徹也 他: "Identification of a mouse TBP-like protein(TLP)distantly related to Prosophila TBP-related factor." Nucl.Acids Res.27. 750-755 (1999)

Tetsuya Obayashi 等人：“与 Prosophila TBP 相关因子密切相关的小鼠 TBP 样蛋白 (TLP) 的鉴定。Nucl.Acids Res.27 (1999)。”

黒川裕美子 他: "A Notable Example of an Evolutionary Conserved Gene : Studies on a Putative DNA Helicase TIP49" DNA seq.10. 37-42 (1999)

Yumiko Kurokawa 等人：“进化保守基因的一个显着例子：对假定 DNA 解旋酶 TIP49 的研究”DNA seq.10 (1999)。

山内淳, 他: "Two formes of avian TBP mRNA gene rated by alfernafive polyadenylation" Biochem.Biophys,Res.Commun.234. 406-411 (1997)

Jun Yamauchi 等人：“通过选择性多聚腺苷酸化评估禽类 TBP mRNA 基因的两种形式”Biochem.Biophys，Res.Commun.234 (1997)。

黒川裕美子 他: "A notable oxample of an evolutionary conserved gene:studies on a patative DNA helicase TIP49" DNA Seq.10. 37-42 (1999)

Yumiko Kurokawa 等人：“进化保守基因的一个值得注意的例子：对帕性 DNA 解旋酶 TIP49 的研究”DNA Seq.10 (1999)。