Putative intestine-specific enhancers located in 5' sequence of the CDX1 gene regulate CDX1 expression in the intestine.
CDX1 is a homeobox transcription factor that plays a critical role in intestinal epithelial cell growth and differentiation. CDX1 gene expression is tightly regulated in a temporal and cell-type specific manner. However, very little is known about the regulatory mechanisms that direct CDX1 gene expression in the intestine. To elucidate these mechanisms, we employed a series of transgenic mouse studies using the 5' flanking sequences of the human CDX1 gene. Transgenic mice containing nucleotides between -5667 and +68 relative to the transcription start site of the CDX1 gene demonstrated ectopic expression of the transgene in the brain and gastric smooth muscle. However, transgenic expression of the nucleotides -15601 to +68 of the CDX1 gene was restricted to the intestinal epithelium, which was identical to endogenous CDX1 gene expression. Taken together, the upstream sequences between -15601 and -5667 contain regulatory elements that direct transgene expression specifically to the intestinal epithelium. Furthermore, DNase I hypersensitivity assays revealed two active chromatin regions in the CDX1 gene (hypertensive sites 1 and 2) located at approximately -5.8 and -6.8 kb upstream of the CDX1 gene, respectively, which may function as potential intestine-specific enhancers.
Rankin
Erinn B
EB
Gastroenterology Div., Dept. of Medicine, Univ. of Pennsylvania, Ste. 600, 415 Curie Blvd., Philadelphia, PA 19104, USA.
Xu
Wei
W
Silberg
Debra G
DG
Suh
EunRan
E
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D017124:Conserved Sequence; D004622:Embryo, Mammalian / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000196:embryology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data
C491273:CDX1 protein, human; C491272:Cdx1 protein, mouse; D018398:Homeodomain Proteins