SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes.
TCF and SOX proteins belong to the high mobility group box transcription factor family. Whereas TCFs, the transcriptional effectors of the Wnt pathway, have been widely implicated in the development, homeostasis and disease of the intestine epithelium, little is known about the function of the SOX proteins in this tissue. Here, we identified SOX9 in a SOX expression screening in the mouse fetal intestine. We report that the SOX9 protein is expressed in the intestinal epithelium in a pattern characteristic of Wnt targets. We provide in vitro and in vivo evidence that a bipartite beta-catenin/TCF4 transcription factor, the effector of the Wnt signaling pathway, is required for SOX9 expression in epithelial cells. Finally, in colon epithelium-derived cells, SOX9 transcriptionally represses the CDX2 and MUC2 genes, normally expressed in the mature villus cells of the intestinal epithelium, and may therefore contribute to the Wnt-dependent maintenance of a progenitor cell phenotype.
Blache
Philippe
P
Institut de Génétique Humaine, CNRS UPR1142, 141 rue de la Cardonille, 34396 Montpellier, Cedex 5, France.
van de Wetering
Marc
M
Duluc
Isabelle
I
Domon
Claire
C
Berta
Philippe
P
Freund
Jean-Noël
JN
Clevers
Hans
H
Jay
Philippe
P
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D000071616:CDX2 Transcription Factor; D002277:Carcinoma / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006609:High Mobility Group Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D055262:Mucin-2; D009077:Mucins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D051176:beta Catenin
D000071616:CDX2 Transcription Factor; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C487514:Cdx2 protein, mouse; D003598:Cytoskeletal Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; C524625:MUC2 protein, human; C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D012313:RNA; D004247:DNA