An endogenous retroviral long terminal repeat is the dominant promoter for human beta1,3-galactosyltransferase 5 in the colon.
LTRs of endogenous retroviruses are known to affect expression of several human genes, typically as a relatively minor alternative promoter. Here, we report that an endogenous retrovirus LTR acts as one of at least two alternative promoters for the human beta1,3-galactosyltransferase 5 gene, involved in type 1 Lewis antigen synthesis, and show that the LTR promoter is most active in the gastrointestinal tract and mammary gland. Indeed, the LTR is the dominant promoter in the colon, indicating that this ancient retroviral element has a major impact on gene expression. Using colorectal cancer cell lines and electrophoretic mobility-shift assays, we found that hepatocyte nuclear factor 1 (HNF-1) binds a site within the retroviral promoter and that expression of HNF-1 and interaction with its binding site correlated with promoter activation. We conclude that HNF-1 is at least partially responsible for the tissue-specific activation of the LTR promoter of human beta 1,3-galactosyltransferase 5. We demonstrate that this tissue-specific transcription factor is implicated in the activation of an LTR gene promoter.
Dunn
Catherine A
CA
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada V5Z 1L3.
Medstrand
Patrik
P
Mager
Dixie L
DL
D001483:Base Sequence; D003106:Colon / Q000201:enzymology* / Q000821:virology*; D003110:Colonic Neoplasms; D020077:Endogenous Retroviruses / Q000235:genetics*; D005091:Exons; D005700:Galactosyltransferases / Q000235:genetics*; D005799:Genes, Dominant; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020079:Terminal Repeat Sequences / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C479886:B3GALT5 protein, human; D005700:Galactosyltransferases