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Gene Review

USF1  -  upstream transcription factor 1

Homo sapiens

Synonyms: BHLHB11, Class B basic helix-loop-helix protein 11, FCHL, FCHL1, HYPLIP1, ...
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Disease relevance of USF1

  • Like hypoxia, inhibitory effects of proteasome inhibitors on hCYP19 expression were mediated by increased binding of USF1/2 to the E-boxes [1].
  • Transcription factors USF1 and USF2 up-regulate gene expression (i.e. , HIV-1 long terminal repeats) via interaction with an E box on their target promoters, which is also a binding site for c-Myc [2].
  • In transiently transfected HeLa or hepatoma cells, USF2a and USF1 homodimers transactivated a minimal promoter with similar efficiency, whereas USF2b, which lacks an internal 67-amino acid domain, was a poor transactivator [3].
  • To explore this possibility, we compared the activities of the ubiquitous USF1 and USF2 proteins in several cell lines derived from either normal breast epithelium or breast tumors [4].
  • Overexpression of USF1 in U87 glioblastoma cells led to an increased activity of the promoter that was partially mediated by the atypical E-box [5].

Psychiatry related information on USF1

  • Genetic association between USF 1 and USF 2 gene polymorphisms and Japanese Alzheimer's disease [6].
  • A mutation that abolishes upstream stimulatory factor binding, either alone or in combination with the alpha EB1 mutation, reduces basal activity of the promoter to approximately 21% of control levels in alpha T3-1 cells and abolishes the decrease in promoter activity seen when Id is overexpressed [7].

High impact information on USF1


Chemical compound and disease context of USF1


Biological context of USF1

  • The USF1 and USF2 proteins contain highly divergent transcriptional activation domains but share extensive homologies in the bHLH-zip region and recognize the same CACGTG DNA motifs [16].
  • USF1 and 2 bound to the E-box motif in the TME and strongly transactivated the PF4 promoter [17].
  • Thus, these studies demonstrate that the novel TME binding transcription factors, USF1 and 2, transactivate rat and human PF4 promoters and may play an important role in megakaryocytic gene expression [17].
  • Whereas USF1 contained only an extended activation domain, USF2 contained both an activation domain and a negative regulatory region [18].
  • In the second trimester, increased O(2) tension promotes proteasomal degradation of USF1/2, resulting in syncytiotrophoblast differentiation and induction of hCYP19 expression [1].

Anatomical context of USF1


Associations of USF1 with chemical compounds

  • Additionally, USF2b was an efficient as USF1 and USF2a homodimers in transactivating the liver-specific pyruvate kinase gene promoter [3].
  • We found that the E-box bound two factors, the USF1/USF2 protein and an unidentified ubiquitous protein which was named factor U [20].
  • Incorporation of a mutant E box into the wild-type CD promoter/chloramphenicol acetyltransferase gene abolished USF binding and reduced the levels of both basal and estrogen-stimulated transcription [21].
  • Upstream stimulatory factor activates the vasopressin promoter via multiple motifs, including a non-canonical E-box [12].
  • These results suggest that one pathway by which apigenin inhibits COX-2 expression is through modulation of USF transcriptional activity [22].

Physical interactions of USF1


Regulatory relationships of USF1


Other interactions of USF1


Analytical, diagnostic and therapeutic context of USF1


  1. O2 enhancement of human trophoblast differentiation and hCYP19 (aromatase) gene expression are mediated by proteasomal degradation of USF1 and USF2. Jiang, B., Mendelson, C.R. Mol. Cell. Biol. (2005) [Pubmed]
  2. USF/c-Myc enhances, while Yin-Yang 1 suppresses, the promoter activity of CXCR4, a coreceptor for HIV-1 entry. Moriuchi, M., Moriuchi, H., Margolis, D.M., Fauci, A.S. J. Immunol. (1999) [Pubmed]
  3. Immunochemical characterization and transacting properties of upstream stimulatory factor isoforms. Viollet, B., Lefrançois-Martinez, A.M., Henrion, A., Kahn, A., Raymondjean, M., Martinez, A. J. Biol. Chem. (1996) [Pubmed]
  4. Loss of USF transcriptional activity in breast cancer cell lines. Ismail, P.M., Lu, T., Sawadogo, M. Oncogene (1999) [Pubmed]
  5. Identification of a non-canonical E-box motif as a regulatory element in the proximal promoter region of the apolipoprotein E gene. Salero, E., Giménez, C., Zafra, F. Biochem. J. (2003) [Pubmed]
  6. Genetic association between USF 1 and USF 2 gene polymorphisms and Japanese Alzheimer's disease. Shibata, N., Ohnuma, T., Higashi, S., Higashi, M., Usui, C., Ohkubo, T., Watanabe, T., Kawashima, R., Kitajima, A., Ueki, A., Nagao, M., Arai, H. J. Gerontol. A Biol. Sci. Med. Sci. (2006) [Pubmed]
  7. Upstream stimulatory factor, a basic-helix-loop-helix-zipper protein, regulates the activity of the alpha-glycoprotein hormone subunit gene in pituitary cells. Jackson, S.M., Gutierrez-Hartmann, A., Hoeffler, J.P. Mol. Endocrinol. (1995) [Pubmed]
  8. Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Pajukanta, P., Lilja, H.E., Sinsheimer, J.S., Cantor, R.M., Lusis, A.J., Gentile, M., Duan, X.J., Soro-Paavonen, A., Naukkarinen, J., Saarela, J., Laakso, M., Ehnholm, C., Taskinen, M.R., Peltonen, L. Nat. Genet. (2004) [Pubmed]
  9. Positional cloning of the combined hyperlipidemia gene Hyplip1. Bodnar, J.S., Chatterjee, A., Castellani, L.W., Ross, D.A., Ohmen, J., Cavalcoli, J., Wu, C., Dains, K.M., Catanese, J., Chu, M., Sheth, S.S., Charugundla, K., Demant, P., West, D.B., de Jong, P., Lusis, A.J. Nat. Genet. (2002) [Pubmed]
  10. An RNA polymerase II transcription factor binds to an upstream element in the adenovirus major late promoter. Carthew, R.W., Chodosh, L.A., Sharp, P.A. Cell (1985) [Pubmed]
  11. USF1 and dyslipidemias: converging evidence for a functional intronic variant. Naukkarinen, J., Gentile, M., Soro-Paavonen, A., Saarela, J., Koistinen, H.A., Pajukanta, P., Taskinen, M.R., Peltonen, L. Hum. Mol. Genet. (2005) [Pubmed]
  12. Upstream stimulatory factor activates the vasopressin promoter via multiple motifs, including a non-canonical E-box. Coulson, J.M., Edgson, J.L., Marshall-Jones, Z.V., Mulgrew, R., Quinn, J.P., Woll, P.J. Biochem. J. (2003) [Pubmed]
  13. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Gregor, P.D., Sawadogo, M., Roeder, R.G. Genes Dev. (1990) [Pubmed]
  14. Variation within the gene encoding the upstream stimulatory factor 1 does not influence susceptibility to type 2 diabetes in samples from populations with replicated evidence of linkage to chromosome 1q. Zeggini, E., Damcott, C.M., Hanson, R.L., Karim, M.A., Rayner, N.W., Groves, C.J., Baier, L.J., Hale, T.C., Hattersley, A.T., Hitman, G.A., Hunt, S.E., Knowler, W.C., Mitchell, B.D., Ng, M.C., O'Connell, J.R., Pollin, T.I., Vaxillaire, M., Walker, M., Wang, X., Whittaker, P., Kunsun, X., Jia, W., Chan, J.C., Froguel, P., Deloukas, P., Shuldiner, A.R., Elbein, S.C., McCarthy, M.I. Diabetes (2006) [Pubmed]
  15. Upstream stimulatory factor 1 associated with familial combined hyperlipidemia, LDL cholesterol, and triglycerides. Coon, H., Xin, Y., Hopkins, P.N., Cawthon, R.M., Hasstedt, S.J., Hunt, S.C. Hum. Genet. (2005) [Pubmed]
  16. Antiproliferative properties of the USF family of helix-loop-helix transcription factors. Luo, X., Sawadogo, M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  17. Upstream stimulatory factors stimulate transcription through E-box motifs in the PF4 gene in megakaryocytes. Okada, Y., Matsuura, E., Tozuka, Z., Nagai, R., Watanabe, A., Matsumoto, K., Yasui, K., Jackman, R.W., Nakano, T., Doi, T. Blood (2004) [Pubmed]
  18. Upstream stimulatory factor regulates major histocompatibility complex class I gene expression: the U2DeltaE4 splice variant abrogates E-box activity. Howcroft, T.K., Murphy, C., Weissman, J.D., Huber, S.J., Sawadogo, M., Singer, D.S. Mol. Cell. Biol. (1999) [Pubmed]
  19. Upstream stimulating factor-1 (USF1) and USF2 bind to and activate the promoter of the adenomatous polyposis coli (APC) tumor suppressor gene. Jaiswal, A.S., Narayan, S. J. Cell. Biochem. (2001) [Pubmed]
  20. The E-box of the human glycophorin B promoter is involved in the erythroid-specific expression of the GPB gene. Camara-Clayette, V., Rahuel, C., Bertrand, O., Cartron, J.P. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  21. Upstream stimulatory factors mediate estrogen receptor activation of the cathepsin D promoter. Xing, W., Archer, T.K. Mol. Endocrinol. (1998) [Pubmed]
  22. Modulation of UVB-induced and basal cyclooxygenase-2 (COX-2) expression by apigenin in mouse keratinocytes: Role of USF transcription factors. Van Dross, R.T., Hong, X., Essengue, S., Fischer, S.M., Pelling, J.C. Mol. Carcinog. (2007) [Pubmed]
  23. Upstream stimulatory factor (USF) as a transcriptional suppressor of human telomerase reverse transcriptase (hTERT) in oral cancer cells. Chang, J.T., Yang, H.T., Wang, T.C., Cheng, A.J. Mol. Carcinog. (2005) [Pubmed]
  24. Upstream stimulatory factor but not c-Myc enhances transcription of the human polymeric immunoglobulin receptor gene. Bruno, M.E., West, R.B., Schneeman, T.A., Bresnick, E.H., Kaetzel, C.S. Mol. Immunol. (2004) [Pubmed]
  25. Insulin-mediated down-regulation of apolipoprotein A5 gene expression through the phosphatidylinositol 3-kinase pathway: role of upstream stimulatory factor. Nowak, M., Helleboid-Chapman, A., Jakel, H., Martin, G., Duran-Sandoval, D., Staels, B., Rubin, E.M., Pennacchio, L.A., Taskinen, M.R., Fruchart-Najib, J., Fruchart, J.C. Mol. Cell. Biol. (2005) [Pubmed]
  26. Cloning and characterization of a novel splicing isoform of USF1. Saito, T., Oishi, T., Yanai, K., Shimamoto, Y., Fukamizu, A. Int. J. Mol. Med. (2003) [Pubmed]
  27. Upstream stimulatory factor regulates Pdx-1 gene expression in differentiated pancreatic beta-cells. Qian, J., Kaytor, E.N., Towle, H.C., Olson, L.K. Biochem. J. (1999) [Pubmed]
  28. Variant forms of upstream stimulatory factors (USFs) control the promoter activity of hTERT, the human gene encoding the catalytic subunit of telomerase. Yago, M., Ohki, R., Hatakeyama, S., Fujita, T., Ishikawa, F. FEBS Lett. (2002) [Pubmed]
  29. Activation of the rat follicle-stimulating hormone receptor promoter by steroidogenic factor 1 is blocked by protein kinase a and requires upstream stimulatory factor binding to a proximal E box element. Heckert, L.L. Mol. Endocrinol. (2001) [Pubmed]
  30. TFII-I regulates induction of chromosomally integrated human immunodeficiency virus type 1 long terminal repeat in cooperation with USF. Chen, J., Malcolm, T., Estable, M.C., Roeder, R.G., Sadowski, I. J. Virol. (2005) [Pubmed]
  31. Human follicle-stimulating hormone receptor (FSH-R) promoter/enhancer activity is inhibited by transcriptional factors, from the upstream stimulating factors family, via E-box and newly identified initiator element (Inr) in FSH-R non-expressing cells. Putowski, L.T., Schillings, W.J., Lee, C.M., Reddy, E.P., Jakowicki, J.A. Gynecol. Endocrinol. (2004) [Pubmed]
  32. The IGF2 receptor is a USF2-specific target in nontumorigenic mammary epithelial cells but not in breast cancer cells. Szentirmay, M.N., Yang, H.X., Pawar, S.A., Vinson, C., Sawadogo, M. J. Biol. Chem. (2003) [Pubmed]
  33. Regulation of telomerase reverse transcriptase gene activity by upstream stimulatory factor. Goueli, B.S., Janknecht, R. Oncogene (2003) [Pubmed]
  34. Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung carcinoma: correlation with dysregulated expression of the transcription factors USF and AP2. Khattar, N.H., Lele, S.M., Kaetzel, C.S. J. Biomed. Sci. (2005) [Pubmed]
  35. Transcriptional regulation of the human reduced folate carrier A1/A2 promoter: Identification of critical roles for the USF and GATA families of transcription factors. Payton, S.G., Liu, M., Ge, Y., Matherly, L.H. Biochim. Biophys. Acta (2005) [Pubmed]
  36. Mitogen-induced expression of the fibroblast growth factor-binding protein is transcriptionally repressed through a non-canonical E-box element. Harris, V.K., Coticchia, C.M., List, H.J., Wellstein, A., Riegel, A.T. J. Biol. Chem. (2000) [Pubmed]
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