Hepatocyte nuclear factors 1alpha and 4alpha control expression of proline oxidase in adult liver.
Adult liver functions are regulated by several hepatocyte nuclear factors (HNFs). HNF4alpha and HNF1alpha are involved in metabolic functions in the liver. The expression of proline oxidase (PO) and proline dehydrogenase was downregulated in the HNF4alpha liver-specific null mice. In addition, the expression of PO was also diminished in the liver derived from HNF1alpha-null mice. The -160 bp proximal promoter region of the PO gene has two HNF4alpha- and HNF1alpha-binding consensus sites. Transactivation, electrophoretic mobility shift and chromatin immunoprecipitation studies revealed that these regions are important for PO promoter activity. These results suggested that HNF4alpha and HNF1alpha regulate proline metabolism in adult liver.
Kamiya
Akihide
A
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bldg 37, Rm 3106B1, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Inoue
Yusuke
Y
Kodama
Tatsuhiko
T
Gonzalez
Frank J
FJ
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D008099:Liver / Q000201:enzymology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D011394:Proline Oxidase / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; C496488:Hnf1a protein, mouse; C496593:Hnf4a protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D011392:Proline; D011394:Proline Oxidase