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Gene Review

Hnf1a  -  HNF1 homeobox A

Rattus norvegicus

Synonyms: HNF-1-alpha, HNF-1A, HNF1, Hepatocyte nuclear factor 1-alpha, Hnf-1, ...
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Disease relevance of Tcf1


Psychiatry related information on Tcf1


High impact information on Tcf1


Chemical compound and disease context of Tcf1


Biological context of Tcf1

  • Binding of the LFB1 dimer to a B-DNA palindromic consensus sequence requires either a conformational change of the DNA (presumably bending), or a rearrangement of the subunits relative to the DNA [13].
  • The helix-turn-helix motif, which has been shown to comprise the DNA recognition helix in the Antp homeodomain, can readily be recognized in the LFB1/HNF1 homeodomain, in spite of an extensive modification of the primary structure [14].
  • A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain [15].
  • However, activity was restored in the presence of the upstream elements, showing that cooperation with factors binding to the CCAAT box and distal elements favors the functional interaction of the liver-specific APF/HNF1 factor with lower-affinity binding sites [16].
  • The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation [16].

Anatomical context of Tcf1

  • Hepatic Nuclear Factor 1 (HNF1, also referred to as LFB1, HP1 or APF) is a liver-specific transcription factor required for the expression of many hepatocyte specific genes [15].
  • Twenty-seven probe sets were present in both CBDL-derived beta2m-/Thy-1+ BM stem cells and control hepatocytes but absent in control beta2m-/Thy-1+ BM stem cells, including Tcf1 and Dbp [17].
  • In vivo footprinting experiments show that the HNF1 binding site is similarly occupied in both adult liver and adult pancreas, in which this gene is practically inactive [18].
  • Furthermore, the hybrid cells failed to express LF-B1-binding activity and mRNA [8].
  • Run-on transcription analysis in isolated nuclei demonstrates that the expression of HNF1 in these cell lines is regulated primarily at the transcriptional level [19].

Associations of Tcf1 with chemical compounds

  • These results suggest that transcription of the pyruvate kinase L gene is not simply regulated by the level of LF-B1 mRNA [20].
  • When intracellular Ca2+ levels are increased or decreased in C cells, by the calcium ionophore A23187, by physiologic concentrations of the P2 purinergic receptor ligand ATP, or by changes in extracellular Ca2+ levels, the promoter activity, RNA levels, and binding of TTF-1 to these genes are, respectively, decreased or increased [21].
  • However, inactivation of either cytokine led to preservation of HNF1 and partially of retinoid X receptor/retinoic acid receptor (RXR/RAR) binding activity [3].
  • Our results show that LFB3 transcripts can be detected in mesoderm-derived cells as soon as they are induced to differentiate into a polarized epithelium, while LFB1 transcripts appear only at a later stage when the three different segments of the nephron become apparent [22].
  • In light of our previous observation that diabetes decreases the abundance of hepatocyte nuclear factor 1 (HNF1), the predominant factor increasing albumin gene transcription, we wondered whether glucose normalization in diabetes would alter HNF1 [5].

Physical interactions of Tcf1

  • The dihedral symmetry of DCoH suggests that binding to the dimerization domain of HNF-1 likely involves the superposition of two-fold rotation axes of the two proteins [23].
  • Constitutive expression of the gene for the cell-specific p48 DNA-binding subunit of pancreas transcription factor 1 in cultured cells is under control of binding sites for transcription factors Sp1 and alphaCbf [24].
  • In gel shift assays, HNF-1alpha and HNF-1beta in H4-II-E extracts bind to the palindromic HNF-1 site [25].
  • Transcription factor tonicity-responsive enhancer-binding protein (TonEBP) which transactivates osmoprotective genes is expressed and upregulated following acute systemic hypertonicity in neurons in brain [26].

Regulatory relationships of Tcf1


Other interactions of Tcf1


Analytical, diagnostic and therapeutic context of Tcf1

  • Titration of HNF1 resulted in an 85% decrease of transcriptional activity, while titration of LF-A1 resulted in only a 40% decrease [29].
  • Gel retardation assay indicated that the different trans-acting factors interacted with three elements and that the transacting protein bound to PKL-I was in fact LF-B1 [33].
  • The L-PK mRNA level in rat liver changed after partial hepatectomy, during development and on intake of a high carbohydrate diet, while the level of LF-B1 mRNA remained unchanged or altered reciprocally [20].
  • We have analyzed the expression pattern of LFB1 and LFB3 in the developing rat kidney by in situ hybridization [22].
  • Immunoprecipitation and immunoblot analyses showed that C2 decreased the level of ubiquitinated HNF1, which was reversed by treatment with MG132, a proteasome inhibitor [34].


  1. The liver-specific transcription factor LF-B1 contains a highly diverged homeobox DNA binding domain. Frain, M., Swart, G., Monaci, P., Nicosia, A., Stämpfli, S., Frank, R., Cortese, R. Cell (1989) [Pubmed]
  2. HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF. Baumhueter, S., Mendel, D.B., Conley, P.B., Kuo, C.J., Turk, C., Graves, M.K., Edwards, C.A., Courtois, G., Crabtree, G.R. Genes Dev. (1990) [Pubmed]
  3. Effects of proinflammatory cytokines on rat organic anion transporters during toxic liver injury and cholestasis. Geier, A., Dietrich, C.G., Voigt, S., Kim, S.K., Gerloff, T., Kullak-Ublick, G.A., Lorenzen, J., Matern, S., Gartung, C. Hepatology (2003) [Pubmed]
  4. Identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a repressor of C/EBPbeta-mediated gene activation. Miau, L.H., Chang, C.J., Shen, B.J., Tsai, W.H., Lee, S.C. J. Biol. Chem. (1998) [Pubmed]
  5. Phlorizin or vanadate treatment reverses impaired expression of albumin and hepatocyte nuclear factor 1 in diabetic rats. Barrera-Hernandez, G., Wanke, I.E., Wong, N.C. Diabetes (1996) [Pubmed]
  6. Identification of gene expression profiles in rat ears with cDNA microarrays. Lin, J., Ozeki, M., Javel, E., Zhao, Z., Pan, W., Schlentz, E., Levine, S. Hear. Res. (2003) [Pubmed]
  7. A myosin-like dimerization helix and an extra-large homeodomain are essential elements of the tripartite DNA binding structure of LFB1. Nicosia, A., Monaci, P., Tomei, L., De Francesco, R., Nuzzo, M., Stunnenberg, H., Cortese, R. Cell (1990) [Pubmed]
  8. Extinction of alpha 1-antitrypsin gene expression in somatic cell hybrids: evidence for multiple controls. Bulla, G.A., DeSimone, V., Cortese, R., Fournier, R.E. Genes Dev. (1992) [Pubmed]
  9. Chimeric liver transcription factors LFB1 (HNF1) containing the acidic activation domain of VP16 act as positive dominant interfering mutants. Denecke, B., Bartkowski, S., Senkel, S., Klein-Hitpass, L., Ryffel, G.U. J. Biol. Chem. (1993) [Pubmed]
  10. The DNA binding activity of the liver transcription factors LFB1 (HNF1) and HNF4 varies coordinately in rat hepatocellular carcinoma. Stumpf, H., Senkel, S., Rabes, H.M., Ryffel, G.U. Carcinogenesis (1995) [Pubmed]
  11. Expression of liver type pyruvate kinase in insulinoma cells: involvement of LF-B1 (HNF1). Noguchi, T., Yamada, K., Yamagata, K., Takenaka, M., Nakajima, H., Imai, E., Wang, Z., Tanaka, T. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  12. Decreased expression levels of rat liver glutathione S-transferase A2 and albumin during the acute phase response are mediated by HNF1 (hepatic nuclear factor 1) and IL6DEX-NP. Whalen, R., Voss, S.H., Boyer, T.D. Biochem. J. (2004) [Pubmed]
  13. The X-ray structure of an atypical homeodomain present in the rat liver transcription factor LFB1/HNF1 and implications for DNA binding. Ceska, T.A., Lamers, M., Monaci, P., Nicosia, A., Cortese, R., Suck, D. EMBO J. (1993) [Pubmed]
  14. The three-dimensional NMR-solution structure of the polypeptide fragment 195-286 of the LFB1/HNF1 transcription factor from rat liver comprises a nonclassical homeodomain. Leiting, B., De Francesco, R., Tomei, L., Cortese, R., Otting, G., Wüthrich, K. EMBO J. (1993) [Pubmed]
  15. A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain. Chouard, T., Blumenfeld, M., Bach, I., Vandekerckhove, J., Cereghini, S., Yaniv, M. Nucleic Acids Res. (1990) [Pubmed]
  16. The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation. Tronche, F., Rollier, A., Bach, I., Weiss, M.C., Yaniv, M. Mol. Cell. Biol. (1989) [Pubmed]
  17. Transcriptomic fingerprinting of bone marrow-derived hepatic beta2m-/Thy-1+ stem cells. Wang, C., Chelly, M.R., Chai, N., Tan, Y., Hui, T., Li, H., Farkas, D.L., Demetriou, A.A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  18. Expression of the L-type pyruvate kinase gene and the hepatocyte nuclear factor 4 transcription factor in exocrine and endocrine pancreas. Miquerol, L., Lopez, S., Cartier, N., Tulliez, M., Raymondjean, M., Kahn, A. J. Biol. Chem. (1994) [Pubmed]
  19. Hepatocyte dedifferentiation and extinction is accompanied by a block in the synthesis of mRNA coding for the transcription factor HNF1/LFB1. Cereghini, S., Yaniv, M., Cortese, R. EMBO J. (1990) [Pubmed]
  20. Alteration in L-type pyruvate kinase gene expression is not associated with the LF-B1 mRNA level. Imai, E., Noguchi, T., Takenaka, M., Yamada, K., Matsuda, T., Monaci, P., Nicosia, A., Tanaka, T. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  21. Thyroid transcription factor 1 is calcium modulated and coordinately regulates genes involved in calcium homeostasis in C cells. Suzuki, K., Lavaroni, S., Mori, A., Okajima, F., Kimura, S., Katoh, R., Kawaoi, A., Kohn, L.D. Mol. Cell. Biol. (1998) [Pubmed]
  22. LFB1 and LFB3 homeoproteins are sequentially expressed during kidney development. Lazzaro, D., De Simone, V., De Magistris, L., Lehtonen, E., Cortese, R. Development (1992) [Pubmed]
  23. High-resolution structures of the bifunctional enzyme and transcriptional coactivator DCoH and its complex with a product analogue. Cronk, J.D., Endrizzi, J.A., Alber, T. Protein Sci. (1996) [Pubmed]
  24. Constitutive expression of the gene for the cell-specific p48 DNA-binding subunit of pancreas transcription factor 1 in cultured cells is under control of binding sites for transcription factors Sp1 and alphaCbf. Knöfler, M., Krapp, A., Hagenbüchle, O., Wellauer, P.K. J. Biol. Chem. (1996) [Pubmed]
  25. Hepatocyte nuclear factor 1 and the glucocorticoid receptor synergistically activate transcription of the rat insulin-like growth factor binding protein-1 gene. Suh, D.S., Rechler, M.M. Mol. Endocrinol. (1997) [Pubmed]
  26. Transcription factor tonicity-responsive enhancer-binding protein (TonEBP) which transactivates osmoprotective genes is expressed and upregulated following acute systemic hypertonicity in neurons in brain. Loyher, M.L., Mutin, M., Woo, S.K., Kwon, H.M., Tappaz, M.L. Neuroscience (2004) [Pubmed]
  27. Amylin gene expression mediated by cAMP/PKA and transcription factors HNF-1 and NFY. Cluck, M.W., Murphy, L.O., Olson, J., Knezetic, J.A., Adrian, T.E. Mol. Cell. Endocrinol. (2003) [Pubmed]
  28. Thresholds for synaptic activation of transcription factors in hippocampus: correlation with long-term enhancement. Worley, P.F., Bhat, R.V., Baraban, J.M., Erickson, C.A., McNaughton, B.L., Barnes, C.A. J. Neurosci. (1993) [Pubmed]
  29. Analysis by cell-free transcription of the liver-specific pyruvate kinase gene promoter. Vaulont, S., Puzenat, N., Kahn, A., Raymondjean, M. Mol. Cell. Biol. (1989) [Pubmed]
  30. Nuclear organization in differentiating oligodendrocytes. Nielsen, J.A., Hudson, L.D., Armstrong, R.C. J. Cell. Sci. (2002) [Pubmed]
  31. In vivo and in vitro regulation of pituitary transcription factor-1 (Pit-1) by changes in the hormone environment. González-Parra, S., Chowen, J.A., García-Segura, L.M., Argente, J. Neuroendocrinology (1996) [Pubmed]
  32. Transcription factor STAT3 in leptin target neurons of the rat hypothalamus. Håkansson, M.L., Meister, B. Neuroendocrinology (1998) [Pubmed]
  33. Identification and characterization of hepatocyte-specific regulatory regions of the rat pyruvate kinase L gene. The synergistic effect of multiple elements. Yamada, K., Noguchi, T., Matsuda, T., Takenaka, M., Monaci, P., Nicosia, A., Tanaka, T. J. Biol. Chem. (1990) [Pubmed]
  34. Ceramide negatively regulates glutathione S-transferase gene transactivation via repression of hepatic nuclear factor-1 that is degraded by the ubiquitin proteasome system. Park, I.N., Cho, I.J., Kim, S.G. Mol. Pharmacol. (2004) [Pubmed]
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