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Gene Review

POU2F1  -  POU class 2 homeobox 1

Homo sapiens

Synonyms: NF-A1, OCT1, OTF-1, OTF1, Oct-1, ...
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Disease relevance of POU2F1

  • The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain [1].
  • Thus, the DRA promoter discriminates against OTF-1 activation at the level of DNA binding in the glioblastoma line [2].
  • The ubiquitous and constitutive octamer transcription factor OTF-1 (Oct 1) is the target of positive regulation by the potent herpes simplex virus trans-activator VP16, which forms a complex with the homeodomain of OTF-1 [3].
  • Glucocorticoid receptor (GR) and octamer transcription factors 1 and 2 (Oct-1/2) interact synergistically to activate the transcription of mouse mammary tumor virus and many cellular genes [4].
  • VP16 forms a complex with cellular factors (Oct1 and host cell factor [HCF]) and TAATGARAT elements (found in all HSV-1 IE promoter/enhancer sequences) to mediate stimulation of IE transcription [5].

High impact information on POU2F1

  • Surprisingly, p38 represents a nuclear form of glyceraldehyde-3-phosphate dehydrogenase, and binding to Oct-1, as well as OCA-S function, is stimulated by NAD(+) but inhibited by NADH [6].
  • We have isolated and functionally characterized a multicomponent Oct-1 coactivator, OCA-S which is essential for S phase-dependent histone H2B transcription [6].
  • Histone gene expression in mammalian cells is codependent upon the Oct-1 transcription factor and its cognate, OCA-S coactivator complex [7].
  • Here we show that the MMTV promoter contains two degenerated octamer motifs immediately upstream of the TATA box that together bind OTF-1 (Oct-1, NFIII) with an affinity similar to the octamer consensus [8].
  • Purification and characterization of OTF-1, a transcription factor regulating cell cycle expression of a human histone H2b gene [9].

Chemical compound and disease context of POU2F1

  • Nonfimbrial, mannose-resistant hemagglutinins (nonfimbrial adhesions [NFA] NFA-1 and NFA-2) were extracted from two agar-grown urinary isolates of Escherichia coli strains 827 (O83:K1:H4) and 54 (O14:K?:H11) [10].

Biological context of POU2F1

  • All of these factors (GR, c-Jun, OCT-1) have transcription activation domains, but STAT3 is required for the observed transcriptional increase [11].
  • Expression of Oct-1 stimulates reporter gene expression from the T and the C-13,910 variant/LPH promoter constructs only when it is co-expressed with HNF1alpha [12].
  • The data suggest that the binding of Oct-1 to the T-13,910 variant directs increased lactase promoter activity and this might provide an explanation for the lactase persistence phenotype in the human population [12].
  • Protein-DNA binding studies on DHS3 revealed that octamer transcription factor 1 (OCT-1) and GATA-4 bound site 7, in vitro, and transient transfection analysis showed that their binding sites were required for silencing activity [13].
  • Antibody supershift and Southwestern blot assays confirmed that the protein binding to the octamer sequence was the ubiquitously expressed transcription factor Oct-1 [14].

Anatomical context of POU2F1


Associations of POU2F1 with chemical compounds

  • Our results indicate that simvastatin and atorvastatin increase the activity of the transcriptional repressor Oct-1 in mononuclear cells, and could thus contribute to decrease the activation of these cells [15].
  • Functional interaction between Oct-1 and retinoid X receptor [20].
  • Furthermore, cotransfected unliganded thyroid hormone receptor enhanced the transactivation by Oct-1, and addition of 3,3',5-tri-iodo-l-thyronine obliterated the stimulatory effects [21].
  • The activation required binding of OTF-1/OTF-2, and C4 could not stimulate transcription by itself, implying a synergistic interaction [22].
  • On denaturing polyacrylamide gels OTF-1 and NFIII exhibit identical mobility [23].

Physical interactions of POU2F1


Regulatory relationships of POU2F1

  • Accordingly, Oct-1 also potently enhances transcriptional activation mediated by a Ser133Ala CREB mutant [26].
  • In this report, we used Oct-1 antisense transformants to determine that Oct-1 represses the interferon-gamma response of the endogenous HLA-DRA gene [27].
  • HCF binds directly to VP16 and this promotes subsequent interaction of the VP16-HCF complex with the POU DNA-binding domain of Oct-1 and selective assembly onto target sites [28].
  • Here we present evidence that the glucocorticoid receptor can negatively regulate OTF-1 function by a mechanism that is independent of DNA binding [3].
  • Oct2 can stimulate transcription in B-cell nuclear extracts and in HeLa nuclear extracts depleted of the ubiquitous factor Oct1 by wheat germ lectin affinity chromatography [29].

Other interactions of POU2F1

  • Based on our biochemical data, we propose a mode of OBF1-Oct1 dimer interaction, suggesting a novel arrangement of the subdomain connectivities [30].
  • GATA-1 and Oct-1 are required for expression of the human alpha-hemoglobin-stabilizing protein gene [31].
  • Both OCT-1 and CAAT motifs are able to confer BRCA1 inducibility in a non-related minimal promoter [32].
  • BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs [32].
  • We had previously shown that the ubiquitous Oct1 and the lymphoid-specific Oct2 transcription factors stimulate transcription at the level of stable preinitiation complex formation [33].

Analytical, diagnostic and therapeutic context of POU2F1


  1. The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain. Assa-Munt, N., Mortishire-Smith, R.J., Aurora, R., Herr, W., Wright, P.E. Cell (1993) [Pubmed]
  2. In vivo footprint analysis of the HLA-DRA gene promoter: cell-specific interaction at the octamer site and up-regulation of X box binding by interferon gamma. Wright, K.L., Ting, J.P. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  3. Functional interference between the ubiquitous and constitutive octamer transcription factor 1 (OTF-1) and the glucocorticoid receptor by direct protein-protein interaction involving the homeo subdomain of OTF-1. Kutoh, E., Strömstedt, P.E., Poellinger, L. Mol. Cell. Biol. (1992) [Pubmed]
  4. Recruitment of octamer transcription factors to DNA by glucocorticoid receptor. Préfontaine, G.G., Lemieux, M.E., Giffin, W., Schild-Poulter, C., Pope, L., LaCasse, E., Walker, P., Haché, R.J. Mol. Cell. Biol. (1998) [Pubmed]
  5. Proteins and cis-acting elements associated with transactivation of the varicella-zoster virus (VZV) immediate-early gene 62 promoter by VZV open reading frame 10 protein. Moriuchi, H., Moriuchi, M., Cohen, J.I. J. Virol. (1995) [Pubmed]
  6. S phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component. Zheng, L., Roeder, R.G., Luo, Y. Cell (2003) [Pubmed]
  7. Gene switching by metabolic enzymes--how did you get on the invitation list? McKnight, S. Cell (2003) [Pubmed]
  8. Ubiquitous transcription factor OTF-1 mediates induction of the MMTV promoter through synergistic interaction with hormone receptors. Brüggemeier, U., Kalff, M., Franke, S., Scheidereit, C., Beato, M. Cell (1991) [Pubmed]
  9. Purification and characterization of OTF-1, a transcription factor regulating cell cycle expression of a human histone H2b gene. Fletcher, C., Heintz, N., Roeder, R.G. Cell (1987) [Pubmed]
  10. Nonfimbrial, mannose-resistant adhesins from uropathogenic Escherichia coli O83:K1:H4 and O14:K?:H11. Goldhar, J., Perry, R., Golecki, J.R., Hoschutzky, H., Jann, B., Jann, K. Infect. Immun. (1987) [Pubmed]
  11. STAT3-dependent enhanceosome assembly and disassembly: synergy with GR for full transcriptional increase of the alpha 2-macroglobulin gene. Lerner, L., Henriksen, M.A., Zhang, X., Darnell, J.E. Genes Dev. (2003) [Pubmed]
  12. T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro. Lewinsky, R.H., Jensen, T.G., Møller, J., Stensballe, A., Olsen, J., Troelsen, J.T. Hum. Mol. Genet. (2005) [Pubmed]
  13. Silencing of Fshr occurs through a conserved, hypersensitive site in the first intron. Hermann, B.P., Heckert, L.L. Mol. Endocrinol. (2005) [Pubmed]
  14. Oct-1 is involved in the transcriptional repression of the gonadotropin-releasing hormone receptor gene. Cheng, C.K., Yeung, C.M., Hoo, R.L., Chow, B.K., Leung, P.C. Endocrinology (2002) [Pubmed]
  15. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase the binding activity and nuclear level of Oct-1 in mononuclear cells. Ortego, M., Hernández, A.G., Bustos, C., Blanco-Colio, L.M., Hernández-Presa, M.A., Tuñón, J., Egido, J. Eur. J. Pharmacol. (2002) [Pubmed]
  16. The human OTF1 locus which overlaps the CD3Z gene is located at 1q22-->q23. Sturm, R.A., Eyre, H.J., Baker, E., Sutherland, G.R. Cytogenet. Cell Genet. (1995) [Pubmed]
  17. The ubiquitous octamer-binding protein(s) is sufficient for transcription of immunoglobulin genes. Johnson, D.G., Carayannopoulos, L., Capra, J.D., Tucker, P.W., Hanke, J.H. Mol. Cell. Biol. (1990) [Pubmed]
  18. Activation of octamer-containing promoters by either octamer-binding transcription factor 1 (OTF-1) or OTF-2 and requirement of an additional B-cell-specific component for optimal transcription of immunoglobulin promoters. Pierani, A., Heguy, A., Fujii, H., Roeder, R.G. Mol. Cell. Biol. (1990) [Pubmed]
  19. Expression of B-lymphocyte-associated transcription factors in human T-cell neoplasms. Marafioti, T., Ascani, S., Pulford, K., Sabattini, E., Piccioli, M., Jones, M., Zinzani, P.L., Delsol, G., Mason, D.Y., Pileri, S.A. Am. J. Pathol. (2003) [Pubmed]
  20. Functional interaction between Oct-1 and retinoid X receptor. Kakizawa, T., Miyamoto, T., Ichikawa, K., Kaneko, A., Suzuki, S., Hara, M., Nagasawa, T., Takeda, T., Mori, J., Kumagai, M., Hashizume, K. J. Biol. Chem. (1999) [Pubmed]
  21. Silencing mediator for retinoid and thyroid hormone receptors interacts with octamer transcription factor-1 and acts as a transcriptional repressor. Kakizawa, T., Miyamoto, T., Ichikawa, K., Takeda, T., Suzuki, S., Mori , J., Kumagai, M., Yamashita, K., Hashizume, K. J. Biol. Chem. (2001) [Pubmed]
  22. Identification of novel ubiquitous and cell type-specific factors that specifically recognize immunoglobulin heavy chain and kappa light chain promoters. Franke, S., Scholz, G., Scheidereit, C. J. Biol. Chem. (1994) [Pubmed]
  23. Anti-OTF-1 antibodies inhibit NFIII stimulation of in vitro adenovirus DNA replication. Pruijn, J.M., van der Vliet, P.C., Dathan, N.A., Mattaj, I.W. Nucleic Acids Res. (1989) [Pubmed]
  24. STAT5 and Oct-1 form a stable complex that modulates cyclin D1 expression. Magné, S., Caron, S., Charon, M., Rouyez, M.C., Dusanter-Fourt, I. Mol. Cell. Biol. (2003) [Pubmed]
  25. Identification of an octamer-binding site controlling the activity of the small breast epithelial mucin gene promoter. Hubé, F., Chooniedass-Kothari, S., Hamedani, M.K., Miksicek, R.J., Leygue, E., Myal, Y. Front. Biosci. (2006) [Pubmed]
  26. Oct-1 potentiates CREB-driven cyclin D1 promoter activation via a phospho-CREB- and CREB binding protein-independent mechanism. Boulon, S., Dantonel, J.C., Binet, V., Vié, A., Blanchard, J.M., Hipskind, R.A., Philips, A. Mol. Cell. Biol. (2002) [Pubmed]
  27. Oct-1 maintains an intermediate, stable state of HLA-DRA promoter repression in Rb-defective cells: an Oct-1-containing repressosome that prevents NF-Y binding to the HLA-DRA promoter. Osborne, A.R., Zhang, H., Fejer, G., Palubin, K.M., Niesen, M.I., Blanck, G. J. Biol. Chem. (2004) [Pubmed]
  28. HCF-dependent nuclear import of VP16. La Boissière, S., Hughes, T., O'Hare, P. EMBO J. (1999) [Pubmed]
  29. Analysis of transcriptional stimulation by recombinant Oct proteins in a cell-free system. Annweiler, A., Zwilling, S., Hipskind, R.A., Wirth, T. J. Biol. Chem. (1993) [Pubmed]
  30. OBF1 enhances transcriptional potential of Oct1. Lins, K., Reményi, A., Tomilin, A., Massa, S., Wilmanns, M., Matthias, P., Schöler, H.R. EMBO J. (2003) [Pubmed]
  31. GATA-1 and Oct-1 are required for expression of the human alpha-hemoglobin-stabilizing protein gene. Gallagher, P.G., Liem, R.I., Wong, E., Weiss, M.J., Bodine, D.M. J. Biol. Chem. (2005) [Pubmed]
  32. BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs. Fan, W., Jin, S., Tong, T., Zhao, H., Fan, F., Antinore, M.J., Rajasekaran, B., Wu, M., Zhan, Q. J. Biol. Chem. (2002) [Pubmed]
  33. The POU domains of the Oct1 and Oct2 transcription factors mediate specific interaction with TBP. Zwilling, S., Annweiler, A., Wirth, T. Nucleic Acids Res. (1994) [Pubmed]
  34. Cytopathic changes and pro-inflammatory cytokines induced by Naegleria fowleri trophozoites in rat microglial cells and protective effects of an anti-Nfa1 antibody. Oh, Y.H., Jeong, S.R., Kim, J.H., Song, K.J., Kim, K., Park, S., Sohn, S., Shin, H.J. Parasite Immunol. (2005) [Pubmed]
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