Hepatocyte nuclear factors (HNFs) are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes. Hepatocyte nuclear factors are expressed predominately in the liver. However, HNFs are also expressed and play important roles in a number of other tissues. Targets of HNFs regulate a variety of different processes, including cytoskeleton reorganization and cell adhesion, cell metabolism, molecular transport and others [1].

Flightless I homolog (FLII) and Dynein, light chain, roadblock-type 1 (DYNLRB1) are cytoskeleton regulators [2], [3]. They are transcriptionally regulated by Forkhead box A2 (HNF3-beta) and Hepatocyte nuclear factor 4, alpha (HNF4-alpha) [4], [5]. Forkhead box A1 (HNF3-alpha) and HNF3-beta regulate the transcription of Apolipoprotein B receptor (APOB48 receptor) [6]. HNF4-alpha activates transcription of Apolipoprotein C-II (APOC2) [7]. APOB48 receptor and APOC2 are known as the regulators of lipid metabolism [7], [8]. HNF3-alpha binds and suppresses NK2 homeobox 1 (TITF1), which is a transcriptionally activated by HNF3-beta [9], [10]. TITF1, in turn, activates transcription of Thyroglobulin [11]. TITF1 and Thyroglobulin along with HNF4-alpha targets, Homeobox B1 (HOXB1) and Homeobox C8 (HOXC8), regulate different developmental processes [4], [12], [13], [14], [15], [16].

HNF1 homeobox A (HNF1-alpha), HNF3-beta and HNF4-alpha regulate the transcription of molecular transporters Retinol binding protein 4, plasma (RBP4), Retinol binding protein 5, cellular (RBP5) and Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 7 (Thyroxine-binding globulin) [5], [14], [17]. HNF1-alpha and HNF3-beta may modulate phagocytosis by regulating Hepatitis A virus cellular receptor 1 (Tim-1) [5], [14].

HNF4-alpha regulates several intracellular processes. HNF4-alpha and HNF3-beta regulate transcription of Ubiquitin-like modifier activating enzyme 6 (UBE1L2) which mediate protein ubiquitination [4]. HNF4-alpha also regulates transcription of Ribonuclease, RNase A family, 3 (ECP (RNase 3)), which participates in RNA catabolism [14], [18]. In addition, HNF4-alpha activates transcription of Golgin B1 (GOLGB1), which promotes organization of Golgi apparatus [5], [19].

HNF3-beta and HNF4-alpha also regulate transcription of Insulin-like growth factor binding protein, acid labile subunit (IGFALS), Carcinoembryonic antigen-related cell adhesion molecule 16 (CEACAM16) and Y box binding protein 1 (YB-1) [5], [14]. YB-1 in turn is a transcriptional regulator of Carcinoembryonic antigen-related cell adhesion molecule 19 (Ceacam19) [20]. IGFALS, CEACAM16 and Ceacam19 promote cell adhesion [21].

HNF4-alpha also controls transcription of Histidyl-tRNA synthetase (SYH) and thereby may modulate protein translation [22], [23].

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