| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
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
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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
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