High impact information on Onecut1

• HNF-6 competed with HNF-3 for binding to the same site in the CYP2C12 promoter [1].
• Using the HNF-6 binding sequence DHWATTGAYTWWD (where W = A or T, Y = T or C, H is not G, and D is not C) determined by sequence comparison and methylation interference, we predicted that HNF-6 will bind to 22 additional hepatocyte-enriched genes [2].
• These studies suggest that HNF-6 may regulate hepatocyte-specific genes and may play a role in epithelial cell differentiation of gut endoderm via regulation of HNF-3(beta) [2].
• The transcriptional activator hepatocyte nuclear factor 6 regulates liver gene expression [2].
• Site-directed mutagenesis of the HNF-6 sites in the HNF-3(beta) and transthyretin promoters diminishes reporter gene expression, suggesting that HNF-6 activates transcription of these promoters [2].

Biological context of Onecut1

• HNF-6 binding activity was also found in the intestinal epithelial cell line HT29, and potential HNF-6 binding sites were present in intestinal sucrase isomaltase, cdx-2 homeodomain protein, and intestinal fatty acid binding protein promoter regions [2].
• Footprinting experiments showed that the GRU binds not only the glucocorticoid receptor (GR), but also ubiquitous [nuclear factor I (NF-I)] and liver-enriched [hepatocyte nuclear factor (HNF)-3, HNF-6, CAAT/enhancer binding protein (C/EBP)] transcription factors [3].
• In protein-DNA interaction studies and in transfection experiments, we found that the liver-enriched transcription factor CCAAT/enhancer-binding protein-alpha (C/EBPalpha) binds to the hnf6 gene and inhibits its expression [4].
• Based on our present results, we propose that adjacent binding sites for NF1 and HNF6 constitute a gene regulatory unit of importance for transducing the female-specific effect of GH in rat liver [5].
• Transfection of mutated and/or deletion constructs showed that HNF6 and NF1 binding markedly enhanced expression in female livers, whereas Stat5 reduces the sex difference by enhancing expression more strongly in male than in female rat liver [5].

Associations of Onecut1 with chemical compounds

• Hepatocyte nuclear factor-6 (HNF-6) contains a single cut domain and a homeodomain characterized by a phenylalanine at position 48 and a methionine at position 50 [6].
• DMSO largely restored hepatic levels of HNF4 and C/EBPalpha, partially suppressed the elevated levels of HNF6, increased HNF1alpha approximately 2-fold, and had little effect on HNF3alpha, HNF3beta, and C/EBPbeta [7].

Other interactions of Onecut1

• Together, the high-density microarray data not only begin to suggest how separate genetic programs in the UB and MM orchestrate the formation of the whole kidney, but also suggest the involvement of heretofore largely unexplored developmental pathways (involving HNF-6, ADAM-10, Celsr-3, DDR2, and other genes) in nephrogenesis [8].

Analytical, diagnostic and therapeutic context of Onecut1

• Electrophoretic mobility shift assays showed more HNF-6 DNA-binding activity in female than in male liver nuclear extracts [1].
• Stimulation of the hnf6 gene by GH therefore involves lifting of the repression exerted by C/EBPalpha in addition to the known GH-induced stimulatory effects of STAT5 (signal transducer and activator of transcription-5) and HNF-4 on that gene [4].

References