hepatocyte nuclear factor 3 alpha


Summary: A forkhead transcription factor that is an essential activator of GLUCAGON gene expression.

Top Publications

  1. Wang Q, Li W, Zhang Y, Yuan X, Xu K, Yu J, et al. Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell. 2009;138:245-56 pubmed publisher
    ..Thus, the role of AR in androgen-independent cancer cells is not to direct the androgen-dependent gene expression program without androgen, but rather to execute a distinct program resulting in androgen-independent growth. ..
  2. Liu Z, Chen S. ER regulates an evolutionarily conserved apoptosis pathway. Biochem Biophys Res Commun. 2010;400:34-8 pubmed publisher
    ..These results elucidate that ER regulates an evolutionarily conserved apoptosis pathway. This opens up new perspectives in the apoptosis of human breast cancer from the evolution of cis-regulatory elements. ..
  3. Motallebipour M, Ameur A, Reddy Bysani M, Patra K, Wallerman O, Mangion J, et al. Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq. Genome Biol. 2009;10:R129 pubmed publisher
    ..We find that ChIP-seq can be used not only to create gene regulatory maps but also to predict molecular interactions and to inform on the mechanisms for common quantitative variation. ..
  4. Nucera C, Eeckhoute J, Finn S, Carroll J, Ligon A, Priolo C, et al. FOXA1 is a potential oncogene in anaplastic thyroid carcinoma. Clin Cancer Res. 2009;15:3680-9 pubmed publisher
    ..Therefore, FOXA1 may be an important oncogene in thyroid tumorigenesis and a potential new therapeutic target for the treatment of anaplastic thyroid cancers. ..
  5. Badve S, Collins N, Bhat Nakshatri P, Turbin D, Leung S, Thorat M, et al. Subcellular localization of activated AKT in estrogen receptor- and progesterone receptor-expressing breast cancers: potential clinical implications. Am J Pathol. 2010;176:2139-49 pubmed publisher
    ..These results suggest that subcellular localization of activated AKT plays a significant role in determining its function in breast cancer, which in part is dependent on TCL1B expression. ..
  6. Pochareddy S, Edenberg H. Identification of a FOXA-dependent enhancer of human alcohol dehydrogenase 4 (ADH4). Gene. 2010;460:1-7 pubmed publisher
    ..6-fold, while one had small but significant effect. The differences in the functional activity in different haplotypes suggest that this region could play an important role in the risk for alcoholism. ..
  7. Huang Q, Li G, Kung A. The -9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPalpha and FOXA1 binding is associated with osteoporosis. Bone. 2009;45:289-94 pubmed publisher
    ..Our data suggest a mechanistic link between rs1230399 and BMD through estrogen ERalpha/FOXA1 signaling pathways driven by long-distance enhancers. ..
  8. Kunisada M, Cui C, Piao Y, Ko M, Schlessinger D. Requirement for Shh and Fox family genes at different stages in sweat gland development. Hum Mol Genet. 2009;18:1769-78 pubmed publisher
    ..The results provide a framework for the further analysis of phased down-stream regulation of gene action, possibly by a signaling cascade, in response to Eda. ..
  9. Nakshatri H, Badve S. FOXA1 in breast cancer. Expert Rev Mol Med. 2009;11:e8 pubmed publisher
    ..Additionally, we discuss modulators of FOXA1 function, ERalpha-FOXA1-GATA3 downstream targets, and potential therapeutic agents that may increase differentiation through FOXA1. ..

More Information


  1. Apparao K, Newman D, Zhang H, Khosla J, Randell S, Sannes P. Temporal changes in expression of FoxA1 and Wnt7A in isolated adult human alveolar epithelial cells enhanced by heparin. Anat Rec (Hoboken). 2010;293:938-46 pubmed publisher
    ..Collectively, these factors may act to modulate differentiation in the adult human pulmonary alveolus. ..
  2. Vaziri Sani F, Kaartinen V, El Shahawy M, Linde A, Gritli Linde A. Developmental changes in cellular and extracellular structural macromolecules in the secondary palate and in the nasal cavity of the mouse. Eur J Oral Sci. 2010;118:221-36 pubmed publisher
    ..The hitherto-unknown innervation pattern of the developing palate was revealed. These findings may be of value for unravelling the pathogenesis of palatal clefting. ..
  3. He H, Meyer C, Shin H, Bailey S, Wei G, Wang Q, et al. Nucleosome dynamics define transcriptional enhancers. Nat Genet. 2010;42:343-7 pubmed publisher
    ..Therefore, quantitative modeling of enhancer structure provides a powerful predictive method to infer the identity of transcription factors involved in cellular responses to specific stimuli. ..
  4. Song Y, Washington M, Crawford H. Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer. Cancer Res. 2010;70:2115-25 pubmed publisher
    ..We conclude that suppression of FOXA1/2 expression is both necessary and sufficient for EMT during PDA malignant progression. ..
  5. Zhang Y, Ali T, Zhou H, D Souza D, Lu Y, Jaffe J, et al. ErbB3 binding protein 1 represses metastasis-promoting gene anterior gradient protein 2 in prostate cancer. Cancer Res. 2010;70:240-8 pubmed publisher
    ..Collectively, our results reveal an EBP1-Foxa-AGR2 signaling circuit with functional significance in metastatic prostate cancer. ..
  6. McMullin R, Dobi A, Mutton L, Orosz A, Maheshwari S, Shashikant C, et al. A FOXA1-binding enhancer regulates Hoxb13 expression in the prostate gland. Proc Natl Acad Sci U S A. 2010;107:98-103 pubmed publisher
    ..These data demonstrate that FOXA1 directly regulates HOXB13 in human prostate epithelial cells, and show that this prostate-specific regulatory mechanism is conserved in mice. ..
  7. Liu N, Niu Y, Wang S, Yu Q, Zhang R, Liu T. [Diagnostic and prognostic significance of FOXA1 expression in molecular subtypes of breast invasive ductal carcinomas]. Zhonghua Yi Xue Za Zhi. 2010;90:1403-7 pubmed
    ..FOXA1 is a promising candidate for clinical identification of luminal A subtype. Prognostic analysis of FOXA1 in low-risk breast cancers may prove to be useful in clinical treatment decision-making. ..
  8. Sun Q, Yu X, Degraff D, Matusik R. Upstream stimulatory factor 2, a novel FoxA1-interacting protein, is involved in prostate-specific gene expression. Mol Endocrinol. 2009;23:2038-47 pubmed publisher
    ..In summary, these data indicate that USF2 is one of the components of the FoxA1/androgen receptor transcriptional protein complex that contributes to the expression of androgen-regulated and prostate-specific genes. ..
  9. Kohler S, Cirillo L. Stable chromatin binding prevents FoxA acetylation, preserving FoxA chromatin remodeling. J Biol Chem. 2010;285:464-72 pubmed publisher
    ..We propose a model whereby stable chromatin binding protects the FoxA DNA-binding domain from acetylation to preserve chromatin binding and remodeling by FoxA factors in the absence of extracellular cues. ..
  10. Fortunati N, Bertino S, Costantino L, De Bortoli M, Compagnone A, Bandino A, et al. Valproic acid restores ER alpha and antiestrogen sensitivity to ER alpha-negative breast cancer cells. Mol Cell Endocrinol. 2010;314:17-22 pubmed publisher
    ..In conclusion, the HDI VPA, inducing ER alpha and FoxA1, confers to MDA-MB 231 cells an estrogen-sensitive "phenotype", restoring their sensitivity to antiestrogen therapy. ..
  11. Belikov S, Astrand C, Wrange O. FoxA1 binding directs chromatin structure and the functional response of a glucocorticoid receptor-regulated promoter. Mol Cell Biol. 2009;29:5413-25 pubmed publisher
    ..Furthermore, the alternative nucleosome arrangement induced by GR and FoxA1 implies this to be determined by constitutive binding of transcription factors rather than by the DNA sequence itself. ..
  12. Lin W, Metzakopian E, Mavromatakis Y, Gao N, Balaskas N, Sasaki H, et al. Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodiencephalic dopaminergic neuron development. Dev Biol. 2009;333:386-96 pubmed publisher
    ..Our data therefore provide new insights into the specification and differentiation of mesodiencephalic dopaminergic neurons and identifies Foxa1 and Foxa2 as essential regulators in these processes. ..
  13. Iacobazzi V, Infantino V, Bisaccia F, Castegna A, Palmieri F. Role of FOXA in mitochondrial citrate carrier gene expression and insulin secretion. Biochem Biophys Res Commun. 2009;385:220-4 pubmed publisher
    ..These results show that FOXA plays a role in the transcriptional regulation of CIC and in insulin secretion. ..
  14. Lee H, Chattopadhyay S, Yoon W, Bahk J, Kim T, Kang H, et al. Overexpression of hepatocyte nuclear factor-3alpha induces apoptosis through the upregulation and accumulation of cytoplasmic p53 in prostate cancer cells. Prostate. 2010;70:353-61 pubmed publisher
    ..The results of the current study suggest a novel function of HNF-3alpha as a killer of malignant prostate cancer cells, which reveals HNF-3alpha as a promising therapeutic molecule for prostate cancers. ..
  15. Gao N, Le Lay J, Qin W, Doliba N, Schug J, Fox A, et al. Foxa1 and Foxa2 maintain the metabolic and secretory features of the mature beta-cell. Mol Endocrinol. 2010;24:1594-604 pubmed publisher
    ..These data demonstrate that Foxa1 and Foxa2 play crucial roles in the development and maintenance of beta-cell-specific secretory and metabolic pathways. ..
  16. Malik S, Jiang S, Garee J, Verdin E, Lee A, O Malley B, et al. Histone deacetylase 7 and FoxA1 in estrogen-mediated repression of RPRM. Mol Cell Biol. 2010;30:399-412 pubmed publisher
  17. Mercier I, Casimiro M, Zhou J, Wang C, Plymire C, Bryant K, et al. Genetic ablation of caveolin-1 drives estrogen-hypersensitivity and the development of DCIS-like mammary lesions. Am J Pathol. 2009;174:1172-90 pubmed publisher
    ..Thus, Cav-1(-/-) null mice are a new preclinical model for studying the molecular paradigm of estrogen hypersensitivity and the development of estrogen-dependent ductal carcinoma in situ lesions. ..
  18. Jacquemier J, Charafe Jauffret E, Monville F, Esterni B, Extra J, Houvenaeghel G, et al. Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer. Breast Cancer Res. 2009;11:R23 pubmed publisher
    ..A panel of three antibodies (Ki67, P53 and GATA3) associated with VPI can significantly improve the traditional prognosticators in predicting outcome for ER-positive breast cancer patients receiving hormonal therapy. ..
  19. GĂ©vry N, Hardy S, Jacques P, Laflamme L, Svotelis A, Robert F, et al. Histone H2A.Z is essential for estrogen receptor signaling. Genes Dev. 2009;23:1522-33 pubmed publisher
    ..Taken together, our results provide strong mechanistic insight into how H2A.Z regulates ERalpha-mediated gene expression and provide a novel link between H2A.Z-p400 and ERalpha-dependent gene regulation and enhancer function. ..
  20. Sano M, Aoyagi K, Takahashi H, Kawamura T, Mabuchi T, Igaki H, et al. Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis. Int J Oncol. 2010;36:321-30 pubmed
  21. Su N, Thiaville M, Awad K, Gjymishka A, Brant J, Yang T, et al. Protein or amino acid deprivation differentially regulates the hepatic forkhead box protein A (FOXA) genes through an activating transcription factor-4-independent pathway. Hepatology. 2009;50:282-90 pubmed publisher
    ..Collectively, the results document that the hepatic FOXA family of genes are differentially regulated by amino acid availability. ..
  22. Li Z, White P, Tuteja G, Rubins N, Sackett S, Kaestner K. Foxa1 and Foxa2 regulate bile duct development in mice. J Clin Invest. 2009;119:1537-45 pubmed publisher
    ..Our data suggest that Foxa1/2 function as terminators of bile duct expansion in the adult liver through inhibition of IL-6 expression. ..
  23. Ang S. Foxa1 and Foxa2 transcription factors regulate differentiation of midbrain dopaminergic neurons. Adv Exp Med Biol. 2009;651:58-65 pubmed
  24. Zhang Y, Liang J, Li Y, Xuan C, Wang F, Wang D, et al. CCCTC-binding factor acts upstream of FOXA1 and demarcates the genomic response to estrogen. J Biol Chem. 2010;285:28604-13 pubmed publisher
    ..We propose that the CTCF-bound boundary elements demarcate active versus inactive regions, building a framework of adjacent chromosome territory that predisposes ERalpha-regulated transcription. ..
  25. Kaestner K. The FoxA factors in organogenesis and differentiation. Curr Opin Genet Dev. 2010;20:527-32 pubmed publisher
  26. Taube J, Allton K, Duncan S, Shen L, Barton M. Foxa1 functions as a pioneer transcription factor at transposable elements to activate Afp during differentiation of embryonic stem cells. J Biol Chem. 2010;285:16135-44 pubmed publisher
  27. Santisteban P, Recacha P, Metzger D, Zaret K. Dynamic expression of Groucho-related genes Grg1 and Grg3 in foregut endoderm and antagonism of differentiation. Dev Dyn. 2010;239:980-6 pubmed publisher
    ..We suggest that Grg expression in the endoderm helps suppress the liver program and find that endodermal competence involves a balance between activators and corepressors. ..
  28. Ademuyiwa F, Thorat M, Jain R, Nakshatri H, Badve S. Expression of Forkhead-box protein A1, a marker of luminal A type breast cancer, parallels low Oncotype DX 21-gene recurrence scores. Mod Pathol. 2010;23:270-5 pubmed publisher
    ..To confirm these findings, further studies in a larger cohort of patients are warranted. ..
  29. Song L, Zhang B, Feng Y, Luo X, Wei X, Xiao X. A role for forkhead box A1 in acute lung injury. Inflammation. 2009;32:322-32 pubmed publisher
    ..These results suggest that FoxA1 may play an important role in ALI by promoting apoptosis of pulmonary epithelial cells. ..
  30. Lanz R, Bulynko Y, Malovannaya A, Labhart P, Wang L, Li W, et al. Global characterization of transcriptional impact of the SRC-3 coregulator. Mol Endocrinol. 2010;24:859-72 pubmed publisher
  31. Strazzabosco M. Foxa1 and Foxa2 regulate bile duct development in mice. J Hepatol. 2010;52:765-7 pubmed publisher
  32. Bernardo G, Lozada K, Miedler J, Harburg G, Hewitt S, Mosley J, et al. FOXA1 is an essential determinant of ERalpha expression and mammary ductal morphogenesis. Development. 2010;137:2045-54 pubmed publisher
    ..These data reveal that FOXA1 is necessary for hormonal responsiveness in the developing mammary gland and ERalpha-positive breast cancers, at least in part, through its control of ERalpha expression. ..
  33. Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, et al. Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours. Breast Cancer Res. 2009;11:R40 pubmed publisher
    ..FOXA1 was a significant predictor of good outcome in breast cancer, whereas GATA-3 was an important luminal marker. The expression of FOXA1 may be used for risk stratification among ERalpha-negative patients. ..
  34. Field Corbett C, English K, O Dea S. Regulation of surfactant protein B gene expression in bone marrow-derived cells. Stem Cells. 2009;27:662-9 pubmed publisher
    ..Furthermore, silencing events, such as methylation, may occur to suppress lung-related gene expression as progenitor cells become committed toward more mature hematopoietic cell phenotypes. ..
  35. Sekiya T, Muthurajan U, Luger K, Tulin A, Zaret K. Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA. Genes Dev. 2009;23:804-9 pubmed publisher
    ..FoxA's distinct nuclear mobility is consistent with its pioneer activity in chromatin. ..
  36. Ye D, Kaestner K. Foxa1 and Foxa2 control the differentiation of goblet and enteroendocrine L- and D-cells in mice. Gastroenterology. 2009;137:2052-62 pubmed publisher
    ..The winged helix factors Foxa1 and Foxa2 are essential members of the transcription factor network that govern secretory cell differentiation in the mammalian gastrointestinal tract. ..
  37. Hu D, Gardner Stephen D, Severi G, Gregory P, Treloar J, Giles G, et al. A novel polymorphism in a forkhead box A1 (FOXA1) binding site of the human UDP glucuronosyltransferase 2B17 gene modulates promoter activity and is associated with altered levels of circulating androstane-3?,17?-diol glucuronide. Mol Pharmacol. 2010;78:714-22 pubmed publisher
    ..In summary, this work identifies FOXA1 as an important regulator of UGT2B17 expression in prostate cancer LNCaP cells and identifies a polymorphism that alters this regulation. ..
  38. Song L, Wei X, Zhang B, Luo X, Liu J, Feng Y, et al. Role of Foxa1 in regulation of bcl2 expression during oxidative-stress-induced apoptosis in A549 type II pneumocytes. Cell Stress Chaperones. 2009;14:417-25 pubmed publisher
    ..These results indicate that Foxa1 plays a pro-apoptotic role by inhibiting the expression of anti-apoptotic gene bcl2. ..
  39. McCune K, Bhat Nakshatri P, Thorat M, Nephew K, Badve S, Nakshatri H. Prognosis of hormone-dependent breast cancers: implications of the presence of dysfunctional transcriptional networks activated by insulin via the immune transcription factor T-bet. Cancer Res. 2010;70:685-96 pubmed publisher
  40. Song L, Xu Z, Zhang C, Qiao X, Huang C. Up-regulation of the HSP72 by Foxa1 in MCF-7 human breast cancer cell line. Biochem Biophys Res Commun. 2009;386:30-4 pubmed publisher
    ..Luciferase reporter showed that Foxa1 also increased the transcription activity of HSP72 promoter. These results indicate an important role for Foxa1 as a novel regulator of expression of HSP72. ..
  41. Eeckhoute J, Lupien M, Meyer C, Verzi M, Shivdasani R, Liu X, et al. Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers. Genome Res. 2009;19:372-80 pubmed publisher
    ..Mechanisms that restrict the activity of shared FOXA1-bound enhancers likely play a significant role in defining the cell-type-specific functions of FOXA1. ..