Transcriptional control of carbohydrate digestion/ absorption-related genes

碳水化合物消化/吸收相关基因的转录控制

• 批准号: 12670063
• 负责人: GODA Toshinao
• 金额: $ 2.18万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670063/
• 关键词: Glucose transporter; Lactase; Gene expression; Coactivator; Nuclear factor; Intestine; Thyroid homone; Development; 転写調節; 核内受容体; 日内リズム; Cdx-2

1.Cloning of coactivators which are associated with the intestinal gene expression : Major transcriptional coactivators, CBP, p300, AFA70, TIF2, SRC-1 were cloned in the rat. Among the coactivators, CBP and p300 were explicitly expressed in the small intestine.2.Transcriptional coactivators which are related with developmental changes in carbohydrate digestion/ absorption-related genes : In the rat, two isoforms of thyroid hormone receptor TR α, i. e., TR α-1 and TR-2, were expressed in the small intestine. During the weaning period (day 13 through 20), the expression of TR α-1 mRNA was temporarily elevated, which was accompanied by parallel rises in the mRNA levels of intestinal glucose transporters (GLUT5, GLUT2, SGLT1). The administration of T3 in this period caused an increase in the gene expression of the glucose transporters. These results suggest that the increase in the gene expression of carbohydrate absorption-related gene during the weaning period is brought about by the act … More ion of TR α-1.3 Transcriptional control through phosphorylation/ dephosphorylation of nuclear transcriptional factors : Phosphorylation of bacterially expressed Cdx-2 caused a decrease in the binding activity of Cdx-2 to the cis-regulatory element in the lactase-phlorizin hydrolase (LPH) gene. In Caco-2 cells, LPH mRNA levels were markedly diminished by the simultaneous administration of T3 and an adenylate cyclase activator, forskolin. The binding of Cdx-2 dimer to the cis regulatory element in the sucrase-isomaltase (SI) gene was stimulated by the dephosphorylation of Cdx-2 through PP1.4. Mechanism leading to diurnal variations of carbohydrate digestion/ absorption-related genes. Nuclear run-on assays using the nuclei prepared from rat small intestine showed that the diurnal variations of the gene expression of SI and glucose transporters involve transcriptional control. The putative clock genes, per2 and BMAL1, were detected in the small intestine, and the mRNA levels of per2 and BMAL1 showed a typical diurnal variation which is altered by the timing of meal feeding. The expression of E4BP4, a transcriptional repressor of SI gene, showed a diurnal variation with the nadir observed around the time of the peak in the expression of carbohydrate digestion/ absorption-related genes. Less

1.与肠道基因表达相关的辅激活因子的克隆：在大鼠中克隆了主要的转录辅激活因子CBP、p300、AFA 70、TIF 2、SRC-1。2.与碳水化合物消化/吸收相关基因发育变化相关的转录辅激活因子：在大鼠甲状腺激素受体TR α的两种异构体，即T1、T2、T3、T4、T5、T6、T7、T8、T10、T11、T12、T13、T14、T16、T17、T18、T19、例如，TR α-1和TR-2在小肠中表达。在断奶期间（第13 ~ 20天），TR α-1 mRNA的表达暂时升高，同时肠道葡萄糖转运蛋白（GLUT 5、GLUT 2、SGLT 1）的mRNA水平也平行升高。在此期间给予T3导致葡萄糖转运蛋白的基因表达增加。这些结果表明，断奶期碳水化合物吸收相关基因的基因表达增加是由这一行为引起的。 ...更多信息 TR α-1.3通过核转录因子的磷酸化/去磷酸化进行转录控制：细菌表达的Cdx-2的磷酸化导致Cdx-2与乳糖酶-根皮苷水解酶（LPH）基因中顺式调节元件的结合活性降低。在Caco-2细胞中，LPH mRNA水平显着减少T3和腺苷酸环化酶激活剂，毛喉素的同时管理。Cdx-2二聚体与蔗糖酶-异麦芽糖酶（SI）基因中的顺式调节元件的结合受到Cdx-2通过PP1.4去磷酸化的刺激。碳水化合物消化/吸收相关基因昼夜变化的机制。利用大鼠小肠制备的细胞核进行的细胞核连续分析表明，SI和葡萄糖转运蛋白基因表达的昼夜变化涉及转录控制。在小肠中检测到假定的时钟基因per 2和BMAL 1，并且per 2和BMAL 1的mRNA水平显示出典型的昼夜变化，其随进食时间而改变。SI基因的转录抑制因子E4 BP 4的表达呈现出昼夜变化，在碳水化合物消化/吸收相关基因表达的峰值附近观察到最低点。少

项目成果

Toshinao Goda: "Regulation of the expression of carbohydrate digestion/absorption-related genes."British Journal of Nutrition. 84. S245-S248 (2000)

Toshinao Goda：“碳水化合物消化/吸收相关基因表达的调节。”英国营养杂志。

合田敏尚 他: "消化と吸収-基礎と臨床-"第一出版. 28 (2000)

Toshihisa Goda 等人：“消化和吸收 - 基础知识和临床研究”第一出版 28 (2000)。

合田敏尚 他: "消化と吸収-基礎と臨床-"第一出版. 27 (2002)

Toshihisa Goda 等人：“消化和吸收 - 基础知识和临床研究”第一出版 27 (2002)。

合田敏尚 他: "スクラーゼ・イソマルターゼ遺伝子の転写調節機構:フルクトース摂取による核内因子Cdx-2の脱リン酸化"消化と吸収. 23(in press). (2000)

Toshihisa Goda 等人：“蔗糖酶和异麦芽糖酶基因的转录调节机制：果糖摄入对核因子 Cdx-2 的去磷酸化”《消化与吸收》23（出版中）。

Goda. T.: "Regulation of the expression of carbohydrate digestion/ absorption-related genes."British Journal of Nutrition. 84. S245-S248 (2000)

戈达。