Regulation of the expression of carbohydrate digestion/absorption-related genes

To explore the underlying molecular mechanism whereby nutrients modulate th e expression of intestinal digestion/absorption-related genes, we have clon ed the 5' flanking regions of two representing disaccharidase genes, i.e. s ucrase-isomaltase (ST) and lactase-phlorizin hydrolase (LPH), and investiga ted whether the binding activity of putative common nuclear factor(s) bindi ng to the cia-elements located in these regions is altered by dietary manip ulations. Orogastric feeding of a sucrose-containing diet to rats caused pa rallel increases in SI mRNA and LPH mRNA levels within 3 h. Among the monos accharides tested, fructose gave rise to the most prominent increase in the mRNA levels of SI and LPH genes, which were accompanied by a coordinate ri se in the mRNA levels of two microvillar hexose transporters, i.e. SGLT1 an d GLUTS. Nuclear run-on assays revealed that fructose, but not glucose, inc reased the transcription of SI, LPH and GLUTS. DNase I footprinting analysi s of the rat LPH gene showed that the protected region conserved the same s equence as the cia-element (CE-LPH1) reported in the pig LPH gene. Electrop horetic mobility shift assay using CE-LPH1 and the related cia-element of S I gene (SIF1) revealed that nuclear extracts from the jejunum of rats fed t he high-starch diet gave greater density of retarded bands than those of ra ts fed the low-starch diet. Force feeding a fructose diet gave rise to an i ncrease in the binding of the dimeric nuclear protein (Cdx-2) to the SIF1 e lement. These results suggest that the cis-elements of CE-LPH1 and SLF1 mig ht be involved in the carbohydrate-induced increases of the transcription o f LPH and SI, presumably through a change in the expression and/or binding activity of Cdx-2.