CDX2 increases SLC7A7 expression and proliferation of pig intestinal epithelial cells.
Nutrient absorption mediated by nutrient transporters expressed in the intestinal epithelium supplies substrates to support intestinal processes, including epithelial cell proliferation. We evaluated the role of Caudal type homeobox 2 (CDX2), an intestine-specific transcription factor, in the proliferation of pig intestinal epithelial cells (IPEC-1) and searched for novel intestinal nutrient transporter genes activated by CDX2. Our cloned pig CDX2 cDNA contains a "homeobox" DNA binding motif, suggesting it is a transcriptional activator. CDX2 overexpression in IPEC-1 cells increased cell proliferation, the percentage of cells in S/G2 phase, and the abundance of transcripts of the cell cycle-related genes Cyclin A2; Cyclin B; Cyclin D2; proliferating cell nuclear antigen; and cell cycle cyclin-dependent kinases 1, 2 and 4, as well as the predicted CDX2 target genes SLC1A1, SLC5A1 and SLC7A7. In addition, luciferase reporter and chromatin immunoprecipitation assays revealed that CDX2 binds directly to the SLC7A7 promoter. This is the first report of CDX2 function in pig intestinal epithelial cells and identifies SLC7A7 as a novel CDX2 target gene. Our findings show that nutrient transporters are activated during CDX2-induced proliferation of normal intestinal epithelial cells.
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China.
Xiang-Guang
XG
Li
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China.
Gao-Feng
GF
Xu
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China.
Zhen-Ya
ZY
Zhai
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China.
Chun-Qi
CQ
Gao
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China.
Hui-Chao
HC
Yan
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China.
Qian-Yun
QY
Xi
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China.
Wu-Tai
WT
Guan
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China.
Song-Bo
SB
Wang
College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China.
Xiu-Qi
XQ
Wang
D000595:Amino Acid Sequence; D027182:Amino Acid Transport System y+ / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000071616:CDX2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013552:Swine
D027182:Amino Acid Transport System y+; D000071616:CDX2 Transcription Factor; D016213:Cyclins; D018844:Cyclin-Dependent Kinases
CDX2; cell proliferation; intestinal epithelial cells; pig; solute carrier family 7 member 7