Transcriptional control of carbohydrate digestion/ absorption-related genes

1.肠道基因表达相关辅活化子的克隆：在大鼠体内克隆了主要的转录辅活化子CBP、p300、AFA70、TIF2、SRC-1。2.与糖消化/吸收相关基因发育变化相关的转录共激活因子：在大鼠的小肠中表达甲状腺激素受体α的两种异构体，即TRα-1和TR-2。在断奶期间(第13~20天)，α-1mRNA表达暂时升高，同时肠道葡萄糖转运蛋白(GLUT5、GLUT2、SGLT1mRNA水平也随之升高。在此期间给予T3可引起葡萄糖转运蛋白基因表达的增加。这些结果表明，断奶期间碳水化合物吸收相关基因的基因表达增加是由ACT…引起的。通过核转录因子的磷酸化/去磷酸化进行转录调控的更多离子：细菌表达的α-2的磷酸化导致CDX-2与乳糖酶根茎苷水解酶基因顺式调节元件的结合活性降低。在Caco-2细胞中，同时给予T3和腺苷环化酶激活剂Forsklin后，LPH的mRNA水平显著降低。通过PP1.4使CDX-2去磷酸化，刺激CDX-2二聚体与蔗糖酶异麦芽糖酶(SI)基因顺式调控元件的结合。导致碳水化合物消化/吸收相关基因日变化的机制。用大鼠小肠制备的细胞核进行的核连续分析表明，SI和葡萄糖转运蛋白基因表达的日变化涉及转录调控。在小肠中检测到可能的时钟基因PER2和BMAL1，PER2和BMAL1的mRNA水平表现出典型的日变化，这种变化随摄食时间的不同而变化。SI基因转录抑制因子E4BP4的表达在碳水化合物消化/吸收相关基因的表达高峰期附近表现出明显的日变化。较少

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