Regulation of lineage-specific transcription of the sucrase-isomaltase gene in transgenic mice and cell lines

Markowitz, A. J.; Wu, Gang; Bader, Andrea; Cui, Zheng; Chen, Lili; Traber, Peter G.

doi:10.1152/ajpgi.1995.269.6.g925

Cited by 32 publications

(49 citation statements)

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“…DNA from tail biopsy samples of the resulting mice was extracted with the QIAamp tissue kit (Qiagen Inc., Valencia, Calif.). The presence of the transgene in mouse genomic DNA was determined by PCR and Southern analysis as described previously (19,20). Transgene founders of the BGSJL/F1 strain (Jackson Laboratory, Bar Harbor, Maine) were bred with normal CD1 mice (Charles River), and offspring were analyzed for the transgene by PCR.…”

Section: Methodsmentioning

confidence: 99%

“…RNA was extracted from multiple tissues using a CsCl gradient method as previously described (19). RNase protection assays were performed using the RPA II kit (Ambion, Austin, Tex.)…”

Section: Methodsmentioning

confidence: 99%

“…This gene encodes an enzyme that is expressed in the brush border of mature enterocytes in a complex developmental pattern (19,20,42). A low level of SI gene expression is first detectable in the mouse embryonic intestine, and this expression remains stable through the first 2 weeks of life after birth.…”

mentioning

confidence: 99%

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A Novel Colonic Repressor Element Regulates Intestinal Gene Expression by Interacting with Cux/CDP

Boudreau

Rings

Swain

et al. 2002

Molecular and Cellular Biology

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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.Morphogenesis of the digestive tract is the result of several steps through development beginning with gross morphogenesis of the organ and then cytodifferentiation of the epithelium and induction of intestine-specific genes in the establishment of the functional adult epithelium (40). In the mouse small intestine, cytodifferentiation occurs between embryonic days 14 and 15 with the transition from a stratified epithelium to a columnar epithelium with nascent villi. Small intestine villi lengthen and crypts form through the first two postnatal weeks. The early development of the mouse colon shows transient similarities to that of the small intestine, with the formation of villus structures. This temporary colonic architecture regresses early during development to form the adult colonic mucosa (39). Early developmental similarities between the small intestine and colon in humans have also been described (21).The sucrase-isomaltase (SI) gene represents a useful model to elucidate the mechanisms of intestinal development. This gene encodes an enzyme that is expressed in the brush border of mature enterocytes in a complex developmental pattern (19,20,42). A low level of SI gene expression is first detectable in the mouse embryonic intestine, and this expression remains stable through the first 2 weeks of life after birth. A similar low and transient level of expression is also detected in the colon during early postnatal life (42). Between days 16 and 17, there is a dramatic induction of SI expression in enterocytes located at the crypt-villus junction in the small intestine (42). Similar transient expression of SI, as well as other intestinal brush border enzymes, has also been observed in the human fetal colon (48). It has been suggested that the mechanisms directing transient SI expression in the colon are recapitulated in the process of human colonic neoplasia, with the reexpression of SI in the majority of colonic adenomatous polyps and adenocarcinomas (4, 9, 45). A comparable recurrence of SI expression was also found in rodent colon tissues subjected to oncogene-mediated transformations (29). Therefore, the delineation of...

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Section: Methodsmentioning

confidence: 99%

“…RNA was extracted from multiple tissues using a CsCl gradient method as previously described (19). RNase protection assays were performed using the RPA II kit (Ambion, Austin, Tex.)…”

Section: Methodsmentioning

confidence: 99%

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A Novel Colonic Repressor Element Regulates Intestinal Gene Expression by Interacting with Cux/CDP

Boudreau

Rings

Swain

et al. 2002

Molecular and Cellular Biology

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“…We fused the 8.5-kb SI promoter (PSI) (41) to the GFP reporter gene (Fig. 3B), and the resulting construct (PSI-GFP) was transfected into Caco-2 cl1 cells.…”

Section: In Vitro Down-regulation Of Si Promoter Activity By Pp Lymphmentioning

confidence: 99%

“…In addition, sucrase isomaltase (SI), a hydrolase expressed in large quantities in the brush border of differentiated small intestine enterocytes (39,40), was reported to be down-regulated in the FAE (24,25). To investigate the mechanism by which SI expression is down-regulated, PP lymphocytes were cocultured with human Caco-2 cl1 cells transfected with SI gene promoter (PSI) (41) fused to the green fluorescent protein (GFP) cDNA. We show that lymphoepithelial-induced down-regulation of SI occurs mainly at the transcriptional level.…”

mentioning

confidence: 99%

Lymphoepithelial Interactions Trigger Specific Regulation of Gene Expression in the M Cell-Containing Follicle-Associated Epithelium of Peyer’s Patches

Bahi

Caliot

Bens³

et al. 2002

The Journal of Immunology

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In the intestine, the follicle-associated epithelium (FAE) of Peyer’s patches (PP) performs Ag sampling as the first step in developing immune responses. Depending on the species, this epithelium contains 10–50% of M cells, which act as regulated gates in epithelial barriers that can be used opportunistically by pathogens to invade their host. However, the mechanisms involved in the differentiation and uptake processes of M cells are not known, in part because their limited number in the intestinal mucosa has hampered molecular and biochemical studies. In this work we provide evidence that PP lymphocytes can themselves modulate gene expression in PP in vivo and in an in vitro model of FAE. Transgenic mice carrying a reporter gene under the control of a modified l-pyruvate kinase promoter (SVPK) exhibit strong transgene expression in PP and FAE, but not in the adjacent villous cells. We used the mouse intestinal epithelial cell line m-ICcl2 transfected with the SVPK promoter fused to β-galactosidase to investigate the direct effect of PP lymphocytes on SVPK promoter activity. β-Galactosidase expression was 4.4-fold higher in transfected m-ICcl2 cells when they were cultured with PP lymphocytes. Conversely, green fluorescent protein expression was 1.8-fold lower in stably transfected differentiated intestinal Caco-2cl1 cells with the sucrase isomaltase promoter fused to green fluorescent protein cDNA when they were cultured with PP lymphocytes, indicating that the in vivo FAE down-regulation of sucrase isomaltase promoter is transcriptionally regulated.

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Characterization of Expression in Mice of a Transgene Containing 3.3 kb of the Human Lactase-Phlorizin Hydrolase (LPH) 5′ Flanking Sequence

et al. 2010

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Background and Aim-The regulation of human intestinal lactase-phlorizin hydrolase remains incompletely understood. One kb of pig and 2 kb of rat 5′-flanking sequence controls correct tissue, cell, topographic, and villus LCT expression. To gain insight into human LCT expression, transgenic mouse lines were generated from 3.3 kb of human LPH 5′ flanking sequence from a lactase persistent individual fused to a human growth hormone (hGH) reporter bounded by an insulator.

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Regulation of lineage-specific transcription of the sucrase-isomaltase gene in transgenic mice and cell lines

Cited by 32 publications

References 0 publications

A Novel Colonic Repressor Element Regulates Intestinal Gene Expression by Interacting with Cux/CDP

A Novel Colonic Repressor Element Regulates Intestinal Gene Expression by Interacting with Cux/CDP

Lymphoepithelial Interactions Trigger Specific Regulation of Gene Expression in the M Cell-Containing Follicle-Associated Epithelium of Peyer’s Patches

Characterization of Expression in Mice of a Transgene Containing 3.3 kb of the Human Lactase-Phlorizin Hydrolase (LPH) 5′ Flanking Sequence

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