hepatocyte nuclear factors


Summary: Hepatocyte nuclear factors are a family of evolutionarily conserved transcription factors that are preferentially expressed in HEPATOCYTES. They play important roles in liver-specific transcription and are critical for CELL DIFFERENTIATION and METABOLISM.

Top Publications

  1. Wang Z, Burke P. Hepatocyte nuclear factor-4? interacts with other hepatocyte nuclear factors in regulating transthyretin gene expression. FEBS J. 2010;277:4066-75 pubmed publisher
    ..These findings provide new insights into the mechanism of the negative transcriptional regulation of the transthyretin gene after injury caused by a decrease in the binding of HNFs and a modulation in their coordinated interactions. ..
  2. Qadri I, Hu L, Iwahashi M, Al Zuabi S, Quattrochi L, Simon F. Interaction of hepatocyte nuclear factors in transcriptional regulation of tissue specific hormonal expression of human multidrug resistance-associated protein 2 (abcc2). Toxicol Appl Pharmacol. 2009;234:281-92 pubmed publisher
    ..The coordinated regulation of xenobiotic transporters and oxidative conjugation may determine the adaptive responses to cellular detoxification processes...
  3. Jonckheere N, Vincent A, Perrais M, Ducourouble M, Male A, Aubert J, et al. The human mucin MUC4 is transcriptionally regulated by caudal-related homeobox, hepatocyte nuclear factors, forkhead box A, and GATA endodermal transcription factors in epithelial cancer cells. J Biol Chem. 2007;282:22638-50 pubmed
    ..The molecular mechanisms governing MUC4 expression during development are, however, unknown. Hepatocyte nuclear factors (HNF), forkhead box A (FOXA), GATA, and caudal-related homeobox transcription factors (TFs) are known to ..
  4. Park Y, Park E, Kim D, Ahn S, Park S, Lee A, et al. Cleaved c-FLIP mediates the antiviral effect of TNF-α against hepatitis B virus by dysregulating hepatocyte nuclear factors. J Hepatol. 2016;64:268-277 pubmed publisher
    ..Taken together, these findings suggest that the anti-apoptotic p22-FLIP serves a novel function of inhibiting HBV transcription, and mediates the antiviral effect of TNF-α against HBV replication. ..
  5. Wang W, Su B, Wang Y. [Gene duplications specific to the amphioxus lineage]. Yi Chuan. 2005;27:143-9 pubmed
  6. Jenkins R, Martin J, Phillips A, Bowen T, Fraser D. Pleiotropy of microRNA-192 in the kidney. Biochem Soc Trans. 2012;40:762-7 pubmed publisher
    ..We describe miR-192-driven anti-and pro-fibrotic effects via the repression of ZEB1 and ZEB2 (zinc finger E-box-binding homeobox proteins 1 and 2), resulting in changes in extracellular matrix deposition and cell differentiation. ..
  7. Pakharukova M, Smetanina M, Ilnitskaya S, Kaledin V, Merkulova T. OAT and 3'MeDAB azo compounds similarly cause liver tumors in GR mice, but differently modify activities of FoxA transcription factors. Bull Exp Biol Med. 2011;152:101-4 pubmed
    ..In contrast to these, 3'MeDAB did not modify FoxA protein activities or the degree of glucocorticoid induction of tyrosine aminotransferase. ..
  8. Li G, Guo G. Role of Class II nuclear receptors in liver carcinogenesis. Anticancer Agents Med Chem. 2011;11:529-42 pubmed
    ..This review summarizes the roles of Class II NRs in liver carcinogenesis and their potential application in the prevention and treatment of HCC. ..
  9. Huang J, Levitsky L, Rhoads D. Boosting native promoter activities with non-adjacent response-element multimers. J Biotechnol. 2010;150:259-67 pubmed publisher
    ..Augmentation of three promoters suggests that this approach is potentially applicable to other promoters for gene therapy and might obviate the need for viral promoters. ..

More Information


  1. Chou C, Chen P, Jeng Y, Cheng A, Huang L, Cheng J. Synergistic effect of radiation and interleukin-6 on hepatitis B virus reactivation in liver through STAT3 signaling pathway. Int J Radiat Oncol Biol Phys. 2009;75:1545-52 pubmed publisher
    ..RT to the liver and longer sustained IL-6 induced HBV reactivation through the STAT3 signal transduction pathway. ..
  2. Wilson M, Barbosa Morais N, Schmidt D, Conboy C, Vanes L, Tybulewicz V, et al. Species-specific transcription in mice carrying human chromosome 21. Science. 2008;322:434-8 pubmed publisher
  3. Lazarevich N, Fleishman D. Tissue-specific transcription factors in progression of epithelial tumors. Biochemistry (Mosc). 2008;73:573-91 pubmed
    ..The main principles of the action of such regulatory systems are reviewed on an example of a network of hepatocyte nuclear factors (HNFs) which play a key role in establishment and maintenance of hepatocytes--the major functional type ..
  4. Funa N, Saldeen J, Akerblom B, Welsh M. Interdependent fibroblast growth factor and activin A signaling promotes the expression of endodermal genes in differentiating mouse embryonic stem cells expressing Src Homology 2-domain inactive Shb. Differentiation. 2008;76:443-53 pubmed
    ..In conclusion, the present results suggest that expression of R522K-Shb enhances certain signaling pathways downstream of FGF and that an interplay between FGF and activin A participates in ES cell differentiation to endoderm. ..
  5. Cheng W, Guo L, Zhang Z, Soo H, Wen C, Wu W, et al. HNF factors form a network to regulate liver-enriched genes in zebrafish. Dev Biol. 2006;294:482-96 pubmed
    ..This observation supports the hypothesis that these four liver-enriched transcription factors form a network in controlling the expression of liver-specific or -enriched genes in the liver. ..
  6. Henkens T, Papeleu P, Elaut G, Vinken M, Rogiers V, Vanhaecke T. Trichostatin A, a critical factor in maintaining the functional differentiation of primary cultured rat hepatocytes. Toxicol Appl Pharmacol. 2007;218:64-71 pubmed
    ..It is suggested that the effects of TSA on CYP gene expression are mediated via controlling the expression of LETFs. ..
  7. Liu Y, Lee W, Wang C, Chao T, Chen Y, Chen J. Regulatory mechanisms controlling human E-cadherin gene expression. Oncogene. 2005;24:8277-90 pubmed
    ..These findings suggested HNF3 plays important roles in the upregulation of the E-cadherin gene and may be able to reduce the motility of metastatic breast cancer cells. ..
  8. Henkens T, Vinken M, Vanhaecke T, Rogiers V. Modulation of CYP1A1 and CYP2B1 expression upon cell cycle progression in cultures of primary rat hepatocytes. Toxicol In Vitro. 2007;21:1253-7 pubmed
    ..Therefore, in order to maintain primary hepatocytes functional in culture, cell cycle inhibition must be achieved. ..
  9. Kamiya A, Gonzalez F, Nakauchi H. Identification and differentiation of hepatic stem cells during liver development. Front Biosci. 2006;11:1302-10 pubmed
    ..The ability to manipulate the proliferation and differentiation of liver stem cells in vitro will greatly aid in analyzing mechanisms of liver development and offers promise in stem cell therapy of liver diseases. ..
  10. Hirai H, Tani T, Kikyo N. Structure and functions of powerful transactivators: VP16, MyoD and FoxA. Int J Dev Biol. 2010;54:1589-96 pubmed publisher
  11. Baier P, Hempel S, Waldvogel B, Baumgartner U. Zonation of hepatic bile salt transporters. Dig Dis Sci. 2006;51:587-93 pubmed
    ..We did not find any differences in nuclear factors or regarding the proteins that could explain the zonal differences in anion transport. ..
  12. Huang W, Weng C. Roles of hepatocyte nuclear factors (HNF) in the regulation of reproduction in teleosts. J Fish Biol. 2010;76:225-39 pubmed publisher
    ..This may help the early development and maturation of the gonad or gamete, sexual maturity or reversion and spawning-regulating mechanisms among fishes to be understood. ..
  13. Glaser S, Wang M, Ueno Y, Venter J, Wang K, Chen H, et al. Differential transcriptional characteristics of small and large biliary epithelial cells derived from small and large bile ducts. Am J Physiol Gastrointest Liver Physiol. 2010;299:G769-77 pubmed publisher
  14. Olek K. Maturity-onset diabetes of the young: an update. Clin Lab. 2006;52:593-8 pubmed
    ..Compared to MODY2, 3, and 5, the remaining subtypes of MODY have a much lower prevalence. Molecular diagnosis has important consequences for prognosis, family screening and therapy. ..
  15. Weedon M, Frayling T. Insights on pathogenesis of type 2 diabetes from MODY genetics. Curr Diab Rep. 2007;7:131-8 pubmed
    ..We review recent studies that suggest that common MODY gene variation contributes modestly to the heritability of type 2 diabetes. ..
  16. Bryzgalov L, Ershov N, Oshchepkov D, Kaledin V, Merkulova T. Detection of target genes of FOXA transcription factors involved in proliferation control. Biochemistry (Mosc). 2008;73:70-5 pubmed
    ..The effect of hepatocarcinogen orthoaminoazotoluene (OAT), which lowers the FOXA activity, on expression of these genes was studied by the real-time PCR. OAT was shown to increase sharply the level of mRNA of the Cul2 and Cdc73 genes...
  17. Njølstad P, Hertel J, Søvik O, Raeder H, Johansson S, Molven A. [Progress in diabetes genetics]. Tidsskr Nor Laegeforen. 2010;130:1145-9 pubmed publisher
    ..How these genetic variants can cause Type 2 diabetes has not been assessed and clinical relevance remains to be shown. So far, genetic findings only affect diagnosis and treatment of monogenic diabetes. ..
  18. Kim M, Lee W, Park E, Park S. Role of hepatocyte nuclear factor-4alpha in transcriptional regulation of C1qTNF-related protein 5 in the liver. FEBS Lett. 2010;584:3080-4 pubmed publisher
    ..Taken together, these results show that hepatocyte nuclear factor-4alpha is involved in transcriptional regulation of CTRP5 in the liver. ..
  19. Olsavsky Goyak K, Laurenzana E, Omiecinski C. Hepatocyte differentiation. Methods Mol Biol. 2010;640:115-38 pubmed publisher
    ..This chapter will briefly review culture methodologies but will primarily focus on hallmark hepatocyte structural, expression and functional markers that characterize the differentiation status of the hepatocyte. ..
  20. Liljeström B, Tuomi T, Isomaa B, Sarelin L, Aktan Collan K, Kaariainen H. Adolescents at risk for MODY3 diabetes prefer genetic testing before adulthood. Diabetes Care. 2007;30:1571-3 pubmed
  21. Jenkins R, Martin J, Phillips A, Bowen T, Fraser D. Transforming growth factor ?1 represses proximal tubular cell microRNA-192 expression through decreased hepatocyte nuclear factor DNA binding. Biochem J. 2012;443:407-16 pubmed publisher
  22. Yamazaki S, Miki K, Takayama T, Hasegawa K, Sata M, Midorikawa Y, et al. Hepatic gene induction in murine bone marrow after hepatectomy. J Hepatol. 2006;44:325-33 pubmed
    ..Circulating signals generated in the AAF/PHx liver might activate this differentiation. ..
  23. Li Q, Zhong W, Qiu Y, Kang X, Sun X, Tan X, et al. Preservation of hepatocyte nuclear factor-4? contributes to the beneficial effect of dietary medium chain triglyceride on alcohol-induced hepatic lipid dyshomeostasis in rats. Alcohol Clin Exp Res. 2013;37:587-98 pubmed publisher
    ..Results suggest that dietary MCT prevents alcohol-induced hepatic lipid accumulation, at least partially, through reducing hepatic polyunsaturated long chain fatty acids and preserving HNF4?. ..
  24. Azmi A, Bao G, Gao J, Mohammad R, Sarkar F. Network insights into the genes regulated by hepatocyte nuclear factor 4 in response to drug induced perturbations: a review. Curr Drug Discov Technol. 2013;10:147-54 pubmed
    ..b>Hepatocyte Nuclear Factors (HNFs) are TFs that have been recognized to play multiple roles in liver physiology...
  25. Rastinejad F, Huang P, Chandra V, Khorasanizadeh S. Understanding nuclear receptor form and function using structural biology. J Mol Endocrinol. 2013;51:T1-T21 pubmed publisher
    ..These emerging structural advances promise to better explain how signals in one domain can be allosterically transmitted to distal receptor domains, also providing much better frameworks for guiding future drug discovery efforts. ..
  26. Ying C, Li Y, Leung C, Robek M, Cheng Y. Unique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogue. Proc Natl Acad Sci U S A. 2007;104:8526-31 pubmed
    ..This mechanism is unique and different from other anti-HBV compounds previously described. ..
  27. Miura H, Tomaru Y, Nakanishi M, Kondo S, Hayashizaki Y, Suzuki M. Identification of DNA regions and a set of transcriptional regulatory factors involved in transcriptional regulation of several human liver-enriched transcription factor genes. Nucleic Acids Res. 2009;37:778-92 pubmed publisher
    ..Finally, co-transfection reporter assays with various combinations of expression vectors for these HNF genes demonstrated the transcriptional activation of the CEBPA gene in a combinatorial manner by these TRFs. ..
  28. Wang S, Tang H, He F, Liu L, Huang F, Zhou T, et al. [On the role of liver-enriched transcription factors in regulating HBV transcription and replication]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2006;37:35-9 pubmed