HNF1alpha upregulates the human AE2 anion exchanger gene (SLC4A2) from an alternate promoter
Malumbres R, Lecanda J, Melero S, Ciesielczyk P, Prieto J, Medina JF.
Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, CIMA, University Clinic and Medical School, University of Navarra, E-31008 Pamplona, Spain.
The human AE2 gene (SLC4A2) is transcribed in a widespread fashion from the upstream promoter, the resultant full-length transcript AE2a being encountered in most tissues. Moreover, alternate promoter sequences within intron 2 may drive tissue-restricted expression of variants AE2b(1) and AE2b(2), mainly in liver and kidney.
AE2b(2) proximal promoter sequences are highly active in transfected liver-derived HepG2 cells and contain an HNF1 motif. Mutation-disruption of this motif dramatically decreased alternate promoter activity in HepG2 cells but not in prostate-derived PC-3 cells. Electromobility shift and supershift assays indicated that HNF1alpha from HepG2 nuclear extracts binds the HNF1 sequence. Transactivation studies in PC-3 cells showed enhanced activity of the wild-type construct upon cotransfection with an HNF1alpha expression plasmid, while activity of the HNF1-mutated construct remained unaffected. Since liver AE2 is putatively involved in the biliary secretion of bicarbonate, HNF1alpha may have a role in increasing bicarbonate secretion in response to certain stimuli.
CITATION Biochem Biophys Res Commun. 2003 Nov 7;311(1):233-40