A novel colonic repressor element regulates intestinal gene expression by interacting with Cux/CDP.
Intestinal gene regulation involves mechanisms that direct temporal expression along the vertical and horizontal axes of the alimentary tract. Sucrase-isomaltase (SI), the product of an enterocyte-specific gene, exhibits a complex pattern of expression. Generation of transgenic mice with a mutated SI transgene showed involvement of an overlapping CDP (CCAAT displacement protein)-GATA element in colonic repression of SI throughout postnatal intestinal development. We define this element as CRESIP (colon-repressive element of the SI promoter). Cux/CDP interacts with SI and represses SI promoter activity in a CRESIP-dependent manner. Cux/CDP homozygous mutant mice displayed increased expression of SI mRNA during early postnatal development. Our results demonstrate that an intestinal gene can be repressed in the distal gut and identify Cux/CDP as a regulator of this repression during development.
Boudreau
François
F
Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rings
Edmond H H M
EH
Swain
Gary P
GP
Sinclair
Angus M
AM
Suh
Eun Ran
ER
Silberg
Debra G
DG
Scheuermann
Richard H
RH
Traber
Peter G
PG
D000375:Aging / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D018938:Caco-2 Cells; D003106:Colon / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D050991:GATA4 Transcription Factor; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins; D006801:Humans; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism*; D013394:Sucrase-Isomaltase Complex / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D019076:Transgenes
C080632:CUX1 protein, human; C000624101:Cux1 protein, mouse; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D013394:Sucrase-Isomaltase Complex