Study on the molecular basis of the response of the digestive tract evoked by nutrients/ food factors

1.小肠中通过TR、GR和RXR的转录控制：糖皮质激素受体GR和甲状腺激素受体TR的配体协同增强人肠细胞系Caco-2中果糖转运蛋白GLUTS的基因表达，这伴随着TR、GR、辅激活因子和乙酰化组蛋白H3和H4在GLUTS基因启动子区域上的结合增加。MAP激酶抑制剂使TR和GR去磷酸化，可增强TR转录活性和GR核转位。在C2BBe 1细胞中的转染测定表明，在细胞中检测到的视黄醇脱氢酶足以将9-顺式视黄醇转化为RXR的配体。通过碳水化合物信号对碳水化合物消化/吸收相关基因的转录控制：高碳水化合物饮食大鼠基因表达的微阵列分析显示，空肠中有52个转录/染色质相关基因上调。在喂食高碳水化合物饮食的小鼠中，蔗糖酶-异麦芽糖酶（SI）基因在空肠中的表达增强，其中乙酰化组蛋白H3和H4以及推定的转录因子（即，Cdx-2和HNF-1在SI基因近端区域表达增强。小鼠喂饲果糖溶液可引起SI基因近端区域乙酰化组蛋白H3和H4的结合增加.通过脂肪酸信号调节靶基因的表达：断奶大鼠饲喂辛酸或油酸可引起PPAR、CBP/p300及其靶基因的基因表达平行增加，即，在围产期突然诱导大鼠小肠CRBPII基因表达时，CRBPII基因近端区域RXR与辅激活因子以及乙酰化组蛋白H3和H4的结合增强。

1. Transcriptional controls through TR, GR and RXR in the small intestine: Ligands of glucocorticoid hormone receptor GR and thyroid hormone receptor TR synergistically enhanced the gene expression of fructose transporter GLUTS in human intestinal cell line, Caco-2, which was accompanied by increases in the binding of TR, GR, coactivators and acetylated histones H3 and H4 on the promoter region of GLUTS gene. Dephosphorylation of TR and GR by MAP kinase inhibitor caused an enhancement of TR transcriptional activity and GR nuclear translocation. Transfection assay in C2BBe1 cell showed that retinal dehydrogenase detected in the cell was sufficient to convert 9-cis retinal to the ligand for RXR.2. Transcriptional controls of carbohydrate digestion/absorption-related genes through a carbohydrate signal: Microarray analysis of the gene expression in rats fed a high carbohydrate diet showed that 52 transcription/chromatin-related genes were up-regulated in jejunum. In mice fed a high carbohydrate diet, the expression of sucrase-isomaltase (SI) gene was enhanced in jejunum, where the bindings of acetylatedhistones H3 and H4 and that of putative transcription factors, i.e., Cdx-2 and HNF-1, were enhanced on the proximal region of SI gene. Feeding fructose solution in mice caused an increase in the binding of acetylated histones H3 and H4 on the proximal region of SI gene.3. Regulation of the expression of target genes through fatty acids signal: Feeding caprylic acid or oleic acid in weanling rats caused a parallel increase in the gene expression of PPAR, CBP/p300 and their target genes, i.e., L-FABP and CRBPII in the jejunum, When CRBPII gene is abruptly induced during the perinatal period in the small intestine of rats, the binding of RXR and coactivators as well as that of acetylated histones H3 and H4 was enhanced on the proximal region of CRBPII gene.