Selected targets of HNF1
Selected targets of HNF1
Two Hepatocyte nuclear factors 1 (HNF1), HNF1-alph a andHNF1-beta, share strong homology in the dimerization domain and DNA-binding domain[1]. Both factors are expressed in polarized epithelia of different organs,including the liver, digestive tract, pancreas, and kidney. HNF1-alpha is notexpressed in lung, whereas HNF1-beta is not expressed in liver. In other organs,HNF1-alpha and HNF1-beta are more or less equally expressed. A significantdifference between HNF1-alpha and HNF1-beta is at the onset of theirexpression during embryonic development [1].
HNF1-alpha plays very important role in liver and metabolic processes. It isinvolved in the regulation of a large set of hepatic genes, including Albumin[2], [3], Cytochrome P450 family 2 subfamily E polypeptide 1 (CYP2E1 ) [4], Cytochrome P450 family 1 subfamily A polypeptide 2 (CYP1A2 ) [5] and Serpin peptidase inhibitor clade A member 1 (Alpha 1-antitrypsin ) [6]. HNF1-alpha is a major regulator ofglucose homeostasis [1]. It regulates transcription of Solute carrier family5 (sodium/glucose cotransporter) member 1 ( SLC5A1 ) [7], Solutecarrier family 2 (facilitated glucose transporter) member 2 ( GLUT2 ) [8]. In addition, HNF1-alpha activates transcription of insulin/energysignaling proteins, specifically of Insulin [9], Insulin-likegrowth factor binding protein 1 ( IBP1 ) [10], and Islet amyloidpolypeptide ( Amylin ) [2].
Both HNF1-alpha and HNF1-beta stimulate transcription of developmentalsignaling proteins, such as Retina and anterior neural fold homeobox ( RAX )[11], Pancreatic and duodenal homeobox 1 ( Pdx-1 (IPF1) ) [12], Nuclear receptor subfamily 5 group A member 2 ( LRH1 ) [13]and others.
In addition, HNF1-alpha and HNF1-beta activate transcription of manycholesterol transporters (Apolipoproteins A1, A2 and B ( APOA1 [14],APOA2 [15], and APOB [11]), ATP-binding cassette,sub-family A member 1 ( ABCA1 ) [16]) and ion channel proteins (Cysticfibrosis transmembrane conductance regulator ( CFTR ) [17], Solutecarrier family 4 anion exchanger member 2 ( SLC4A2 ) [18], Polycystickidney disease 2 ( Polycystin 2 ) [19] and others).
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