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The mammalian  Caudal -related homeobox transcription factor 2 (CDX2) plays a key role in the homeobox regulatory network and is essential in regulating the expression of several homeobox ( HOX)  genes during embryonic development, particularly in the gut. Genome-wide CDX2 chromatin immunoprecipitation analysis and expression data from Caco2 cells also suggests a role for CDX2 in the regulation of  HOXB4  gene expression in the intestinal epithelium. Thus, the aim of this study was to investigate whether  HOXB4  gene expression is regulated by CDX2 in the intestinal epithelium. We demonstrated binding of CDX2 to four different CDX2 binding sites in an enhancer region located upstream of the  HOXB4  transcription start site. Mutations in the CDX2 binding sites reduced  HOXB4  gene activity, and knock down of endogenous CDX2 expression by shRNA reduced  HOXB4  gene expression. This is the first report demonstrating the CDX2 regulation of HOXB4 gene expression in the developed intestinal epithelium, indicating a possible role for HOXB4 in intestinal homeostasis.

HOXB4 Gene Expression Is Regulated by CDX2 in Intestinal Epithelial Cells