Target genes of RORα which controls postnatal development of cerebeller Purkinje cells

控制小脑浦肯野细胞出生后发育的 RORα 靶基因

• 批准号: 09680777
• 负责人: MATSUI Takashi
• 金额: $ 1.98万
• 依托单位: UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680777/
• 关键词: RORα; nuclear receptor; transcription regulation; Purkinje cells; promoter; 小脳プルキン工細胞; 生後分化; 糖脂質; コアクチベータ-; プルキンエ細胞

We analyzed regulatory mechanisms of transcription of three genes, Pcp-2, prosaposin and 5-lipoxygenase genes, which are expressed in the Purkinje cells and contain a RORα-responsive elemenet (RORE). RORα-dependent transcription of the Pcp-2 gene which does not contain a glucocorticoid responsive element was shown to be repressed by glucocorticoid receptor (GR). Reciprocally, GR-dependent transcription of MMTV promoter was repressed by RORα. Regions essential for the transcriptional antagonism was mapped to the N-terminus of GR and the C-terminus of RORα, respectively. Since RORα and GR did not directly interact each other, it was suggested that a novel mediator common for RORα and GR confers the transcriptional antagonism between them.Prosaposin gene (pSAP) contains a RORE which is efficiently bound with RORα. Although RORα activated transcription of the tk gene promoter linked with the RORE of pSAP gene, it failed to activate transcription of pSAP gene both in P19 and HeLa cells. In contrast, although GRE linked to pSAP gene failed to activate its transcription in P19, it activated the transcription in HeLa cells. These results indicated that transcriptional activation by nuclear receptors is dependent both on type of promoter and cell-type. Since promoters of eukaryptic genes show a structural variety, basal transcriptional complex formed on the promoter might differ from one to another. Nuclear receptor bound with its cognate responsive element interact differently to the basal transcription complex.Transcription of 5-lipoxygenase (5-LO) gene has been demonstrated to be repressed by RORα. We recently observed that the transcriptional repression results from suppression of EGR1 function which actc as a transactivator of this gene.

我们分析了三种基因的转录机制，即pcp-2，prosaposin和5-脂氧合酶基因，这些基因在purkinje细胞中表达并包含RORα反应性leemenet（Rore）。不包含糖皮质激素反应元件的PCP-2基因的RORα依赖性转录被证明是通过糖皮质激素受体（GR）再现的。 RORα以相互依赖的MMTV启动子的GR依赖性转录。转录拮抗作用必不可少的区域分别映射到GR的N端和RORα的C端。由于RORα和GR并未直接相互作用，因此建议一种新型的RORα和GR共同的介体赋予它们之间的转录拮抗作用。ProsaposinGene（PSAP）包含有效与RORα结合的RORE。尽管RORα激活了与PSAP基因rore相关的TK基因启动子的转录，但它未能激活p19和HeLa细胞中PSAP基因的转录。相反，尽管与PSAP基因相关的GRE未能激活其在p19中的转录，但它激活了HeLa细胞中的转录。这些结果表明，核接收器的转录激活取决于启动子类型和细胞类型的类型。由于真核命令基因的启动子显示出结构性的多样性，因此在启动子上形成的基本转录复合物可能因其而异。与基本转录复合物相互作用的核接收器与基本转录复合物的相互作用不同。5-脂氧合酶（5-li）基因的转录已被RORα复制。我们最近观察到，转录表示是由抑制EGR1功能的抑制作用，该功能是该基因的反式激活剂。

项目成果

S.Sashihara: "Oncogenes and Signal Transduction Pathways Involved in Regulation of Na^+ Channel Expression" Critical Reviews in Oncogenesis. 9. 19-24 (1998)

S.Sashihara：“致癌基因和信号转导途径参与 Na^ 通道表达的调节”肿瘤发生中的批判性评论。

F. Kayama et. al.: "Proinflammatory cytokines and interleukin-6 in the renal response to bacterial endotoxin."Cytokine. 9. 688-695 (1997)

F. Kayama 等。

松井隆司: "小脳形成とオーファン核内レセプターRORα"蛋白質・核酸・酵素. 42. 2039-2048 (1997)

Takashi Matsui：“小脑形成和孤儿核受体 RORα”蛋白质、核酸和酶。 42. 2039-2048 (1997)

T.Matsui: "Transcriptional regulation of a Purkinje cell-specific gene through a functional interaction between RORα and RAR." Genes to Cells. 2. 263-272 (1997)

T.Matsui：“通过 RORα 和 RAR 之间的功能相互作用对浦肯野细胞特异性基因进行转录调节。”2. 263-272 (1997)

M. Ogata et al: "Carrageenan primes leukocytes to enhance lipopolysaccharide-induced tumor necrosis factor alpha production."Infection and Immunity. 67. 3284-3289 (1999)

M. Ogata 等人：“卡拉胶启动白细胞以增强脂多糖诱导的肿瘤坏死因子 α 的产生。”感染和免疫。