Identification of target genes of the transcription factor HNF1β and HNF1α in a human embryonic kidney cell line

Hepatocyte nuclear factor 1beta (HNF1β, TCF2) is a tissue-specific transcription factor whose mutation in humans leads to renal cysts, genital malformations, pancreas atrophy and maturity onset diabetes of the young (MODY5). Furthermore, HNF1β overexpression has been observed in clear cell cancer of the ovary. To identify potential HNF1β target genes whose activity may be deregulated in human patients, we established a human embryonic kidney cell line (HEK293) expressing HNF1β conditionally. Using Flp recombinase, we introduced wild type or mutated HNF1β at a defined chromosomal position allowing a most reproducible induction of the HNF1β derivatives upon tetracycline addition. By oligonucleotide microarrays we identified 25 HNF1β-regulated genes. By an identical approach, we identified that the related transcription factor HNF1α (TCF1) affects only nine genes in HEK293 cells and thus is a less efficient factor in these kidney cells. The HNF1β target genes dipeptidyl peptidase 4 (DPP4), angiotensin converting enzyme 2 (ACE2) and osteopontin (SPP1) are most likely direct target genes, as they contain functional HNF1 binding sites in their promoter region. Since nine of the potential HNF1β target genes are deregulated in clear cell carcinoma of the ovary, we propose that HNF1β overexpression in the ovarian cancer participates in the altered expression pattern.