cis Elements of the Villin Gene Control Expression in Restricted Domains of the Vertical (Crypt) and Horizontal (Duodenum, Cecum) Axes of the Intestine*

By B. Madison, Laura Dunbar, X. Qiao, K. Braunstein, Evan M. Braunstein, D. Gumucio. Journal of Biological Chemistry, 2002

777 citations recorded by the source corpus.

Villin, an actin bundling protein found in the apical brush border of absorptive tissues, is one of the first structural genes to be transcriptionally activated in the embryonic intestinal endoderm. In the adult, villin is broadly expressed in every cell of the intestinal epithelium on both the vertical axis (crypt to villus tip) and the horizontal axis (duodenum through colon) of the intestine. Here, we document that a 12.4-kilobase region of the mouse villin gene drives high level expression of two different reporter genes (LacZ and Cre recombinase) within the entire intestinal epithelium of transgenic mice. Deletion of a portion of this transgene results in reduction of β-galactosidase activity in restricted domains of the small intestine (duodenum) and large intestine (cecum). In addition, expression is reduced in the crypt compartment throughout the intestine. Thus, the global expression pattern of villin in the intestine is apparently the consequence of an amalgam of distinct and individual domain-specific control processes. That is, expression of villin in the duodenum and cecum requires different regulatory sequences than the rest of the intestine, and the expression of villin in crypts is regulated by different circuitry than expression of villin on villus tips.

Subfields: Genetics, Pathology and Forensic Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/6f96acaf2fbc8a1586caa2f7878280f8b29aeee4

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Citations in the corpus

The Host Shapes the Gut Microbiota via Fecal microRNA (2016, neutral): “Cre recombinase under the direction of the villin 1 promoter (Madison et al., 2002).”
gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. (2009, methodology): “Mice and CAC Model To delete Stat3 in IECs, we crossed Stat3lox/loxmice (termed Stat3flox) (Takeda et al., 1998) to villin-Cre transgenic mice (Madison et al., 2002), which were backcrossed for four generations on an FVB background before intercrossing to generate compound mutant…”
STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing (2009, methodology): “Accordingly, mice with floxed STAT3 alleles (Takeda et al., 1998) were crossbred to Villin-Cre mice expressing the Cre-recombinase specifically in IECs (Madison et al., 2002).”
IL-6 and STAT3 are required for survival of intestinal epithelial cells and development of colitis associated cancer (2009, methodology): “To determine the contribution of Stat3 in IECs to CAC tumorigenesis, we generated mice with a conditional Stat3 deletion in enterocytes ( Stat3 D IEC mice) by crossing Stat3 F/F mice (Takeda et al., 1999) with villin -Cre mice (Madison et al., 2002).”
XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease (2008, positive): “…Enteritis Xbp1flox/flox mice were generated by targeting loxP sites to introns flanking exon 2, and bred onto Villin (V) -Cre transgenic mice (see Figures S1A–S1C available online), that directs Cre recombinase activity specifically to small and large intestinal epithelium (Madison et al., 2002).”