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Forkhead box transcription factors Foxa1 and Foxa2 are important regulators of Muc2 mucin expression in intestinal epithelial cells
Ist Teil von
Biochemical and biophysical research communications, 2008-05, Vol.369 (4), p.1108-1113
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2008
Quelle
MEDLINE
Beschreibungen/Notizen
The mucin Muc2 is the main component of the intestinal mucus layer and thus plays important roles in intestinal protection. Therefore, it is important to understand its regulation during goblet cell differentiation. Foxa1 and Foxa2 forkhead box transcription factors (TFs) participate in transcriptional programs governing intestinal cell differentiation. Using immunohistochemistry, we showed a spatio-temporal pattern of expression of both TFs in developing and adult mouse intestine and their expression in Muc2-expressing intestinal cells. Down-regulation of Foxa1 and Foxa2 by RNA interference in cultured intestinal cells decreased
Muc2 mRNA level by half, and abolished Muc2 protein expression. Chromatin immunoprecipitation and gel shift assays showed that these two TFs directly bind to the
Muc2 promoter. Co-transfection experiments indicated that both TFs activate the
Muc2 promoter and that mutations of three Foxa
cis-elements inhibit
Muc2 transactivation. In conclusion, this work identifies Foxa1 and Foxa2 as important regulators of
Muc2 expression in the intestine.