Intestinal apolipoprotein AI gene transcription is regulated by multiple distinct DNA elements and is synergistically activated by the orphan nuclear receptor, XXXX .

@entity1 @entity5907 @entity2036 @entity1675 @entity12436 @entity157 @entity694
We have used apolipoprotein genes to investigate the signal transduction mechanisms involved in the control of intestinal specific gene expression. The @entity1 @entity1675 , @entity12436 , and apoAIV genes are tandemly organized within a 15-kb DNA segment and are expressed predominantly in the liver and intestine. Transient transfection of various @entity1 @entity1675 gene plasmid constructs into @entity1 @entity157 (HepG2) and @entity694 (Caco-2) cells showed that @entity1675 gene transcription is under the control of two separate and distinct cell-specific promoters. The region between @entity2036 -192 and -41 is essential for expression in HepG2 cells, whereas the region from -595 to -192 is essential for expression in Caco-2 cells. A third 0.6 kb DNA fragment in the @entity12436 gene promoter region, approximately 5 kb down-stream from the @entity1 @entity1675 gene, enhances transcription mediated by either of these two tissue-specific @entity1675 promoters. In Caco-2 cells, expression of the @entity1675 gene and activation by the distal enhancer required the presence of a nuclear hormone receptor response element (NHRRE) located in the -214 to -192 @entity1675 promoter region. Overexpression of the orphan receptor @entity5907 ( @entity5907 ), which binds to the NHRRE, dramatically stimulates @entity1675 gene expression in Caco-2 cells but not in HepG2 cells. Maximal stimulation of transcription by @entity5907 in Caco-2 cells required the presence of both the intestinal specific promoter, the NHRRE, and distal enhancer elements. Transactivation by @entity5907 thus appears to result from functional synergy between the NHRRE binding @entity5907 and distal DNA elements containing intestinal-specific DNA binding activities. The @entity1675 gene provides a model system to define the mechanism(s) governing intestinal cell specific gene regulation and the role of nuclear hormone receptors in the establishment and regulation of enterocytic gene transcription.
