Homeodomain transcription factor CDX1 is required for the transcriptional induction of PPARγ in intestinal cell differentiation

Abstract 

The caudal-associated homeobox transcription factor, CDX1, performs critical functions in intestinal cell proliferation, differentiation, and neoplasia. In this study, we have identified the molecular mechanism underlying the CDX1-mediated regulation of intestinal cell differentiation. CDX1 enhanced the expression of PPARγ gene, a master transcriptional regulator of intestinal differentiation, at the transcriptional level, via functional interaction with CCAAT/enhancer-binding protein alpha (C/EBPα). Butyrate, an intestinal differentiation inducer, increased the protein interaction of CDX1 and C/EBPα, thereby resulting in a significant increase in PPARγ expression. These results show that the regulation of target gene expression for intestinal determination is dependent on a transcriptional cascade of CDX1, C/EBPα, and PPARγ.

Structured summary

MINT-6800304: CDX1 (uniprotkb:P47902) physically interacts (MI:0218) with CEBPalpha (uniprotkb:P49715) by pull down (MI:0096)

MINT-6800330: CDX1 (uniprotkb:P47902) physically interacts (MI:0218) with CEBPalpha (uniprotkb:P49715) by two hybrid (MI:0018)

MINT-6800315: CEBPalpha (uniprotkb:P49715) physically interacts (MI:0218) with CDX1 (uniprotkb:P47902) by anti bait co-immunoprecipitation (MI:0006)

Abbreviations: PPARγ, peroxisome proliferator-activated receptor gamma, C/EBPα, CCAAT/enhancer-binding protein alpha, SCFA, short-chain fatty acids, ALP, alkaline phosphatase activity

Keywords: Butyrate, CDX1, PPARγ, C/EBPα, Intestinal differentiation