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Gene Review

Pou3f2  -  POU domain, class 3, transcription factor 2

Mus musculus

Synonyms: 9430075J19Rik, A230098E07Rik, Brain-2, Brain-specific homeobox/POU domain protein 2, Brn-2, ...
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Disease relevance of Pou3f2


High impact information on Pou3f2

  • Such roles have been most clearly established for Pit-1, which is required for formation of somatotropes, lactotropes, and thyrotropes in the anterior pituitary gland, and for Brn-2, which is critical for formation of magnocellular and parvocellular neurons in the paraventricular and supraoptic nuclei of the hypothalamus [5].
  • Together these data strongly indicate that Brn-2 function largely overlaps with that of Oct-6 in driving the transition from promyelinating to myelinating Schwann cells [6].
  • Brn-1 and Brn-2 share crucial roles in the production and positioning of mouse neocortical neurons [7].
  • POU homeodomain proteins Brn-1 and Brn-2 are coexpressed in the developing neocortex, both in the late precursor cells and in the migrating neurons [7].
  • We provide evidence that, during development of the Sim1 mutant hypothalamus, the prospective PVN/SON region fails to express Brn2 [8].

Chemical compound and disease context of Pou3f2

  • Expression of Brn-2 is activated when P19 embryonal carcinoma cells are induced to differentiate into neural cells with retinoic acid (RA) [9].
  • Reversible oxidation sensitivity of N-Oct-3 DNA binding activity was seen when melanoma extracts and recombinant Brn-2 protein were treated with a variety of metals, hydrogen peroxide and the cysteine disulphide bond forming agent diamide [10].
  • Brn-2 C-terminal antibody Western blot analysis of melanoma cell line nuclear extracts prepared using a combination of sodium dodecyl sulphate and NP-40 detergent cell lysis procedures demonstrated the formation of N-Oct-5 DNA binding activity via N-terminal proteolytic clipping of Brn-2/N-Oct-3 [10].

Biological context of Pou3f2


Anatomical context of Pou3f2

  • Brain-2 (Brn-2), a Class III POU transcription factor, plays an important role in the development of the neocortex and the establishment of neural cell lineage [1].
  • Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2 [15].
  • Strikingly, deletion of the Brn-2 genomic locus results in loss of endocrine hypothalamic nuclei and the posterior pituitary gland [15].
  • Neurons comprising the endocrine hypothalamus are disposed in several nuclei that develop in tandem with their ultimate target the pituitary gland, and arise from a primordium in which three related class III POU domain factors, Brn-2, Brn-4, and Brn-1, are initially coexpressed [15].
  • Ectopic expression of Brn2 plus HoxA1 but not either factor alone, is sufficient to induce efficient expression from the endogenous Pax3 promoter in P19 EC stem cells under conditions where they would not otherwise express Pax3 [14].

Associations of Pou3f2 with chemical compounds

  • The mammalian Brain-2 gene had alanine, glycine, proline, and glutamine repeats, which were missing in the nonmammalian homologue [16].
  • In P19 cells, the 0.5 kb upstream region of Brn-2 was sufficient for the transcriptional activation during RA-induced differentiation [9].
  • Consistent with these findings, N2A cells transfected with Brn2 formed octamer-binding complexes containing N-Oct3, the transcriptionally active form of Brn2, whereas complexes formed in C6 cells contained only N-Oct5A and N-Oct5B [17].
  • These include retinoic acid receptors, the epidermal growth factor receptor and the transcription factors Oct-3 and Brn-2 [18].
  • In mice whose bile ducts had been ligated 24 h before the administration of the manganese compound, we observed, 1 week after the injection, an amount of manganese accumulated in the brain 2 times higher than in normal mice [19].

Regulatory relationships of Pou3f2


Other interactions of Pou3f2


Analytical, diagnostic and therapeutic context of Pou3f2


  1. The neuronal POU transcription factor Brn-2 interacts with Jab1, a gene involved in the onset of neurodegenerative diseases. Huang, Y.T., Iwamoto, K., Kurosaki, T., Nasu, M., Ueda, S. Neurosci. Lett. (2005) [Pubmed]
  2. Analysis of tumor progression by transcriptional profiling of mouse MK16 cell lines transformed with human papillomavirus type 16 E6 and E7 oncogenes and activated H-ras. Smahel, M., Smahelová, J., Tejklová, P., Tachezy, R., Jelínek, F. Oncol. Rep. (2005) [Pubmed]
  3. Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin. Goodall, J., Martinozzi, S., Dexter, T.J., Champeval, D., Carreira, S., Larue, L., Goding, C.R. Mol. Cell. Biol. (2004) [Pubmed]
  4. Preferential differentiation of P19 mouse embryonal carcinoma cells into smooth muscle cells. Use of retinoic acid and antisense against the central nervous system-specific POU transcription factor Brn-2. Suzuki, T., Kim, H.S., Kurabayashi, M., Hamada, H., Fujii, H., Aikawa, M., Watanabe, M., Watanabe, N., Sakomura, Y., Yazaki, Y., Nagai, R. Circ. Res. (1996) [Pubmed]
  5. POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease. Andersen, B., Rosenfeld, M.G. Endocr. Rev. (2001) [Pubmed]
  6. The POU proteins Brn-2 and Oct-6 share important functions in Schwann cell development. Jaegle, M., Ghazvini, M., Mandemakers, W., Piirsoo, M., Driegen, S., Levavasseur, F., Raghoenath, S., Grosveld, F., Meijer, D. Genes Dev. (2003) [Pubmed]
  7. Brn-1 and Brn-2 share crucial roles in the production and positioning of mouse neocortical neurons. Sugitani, Y., Nakai, S., Minowa, O., Nishi, M., Jishage, K., Kawano, H., Mori, K., Ogawa, M., Noda, T. Genes Dev. (2002) [Pubmed]
  8. Development of neuroendocrine lineages requires the bHLH-PAS transcription factor SIM1. Michaud, J.L., Rosenquist, T., May, N.R., Fan, C.M. Genes Dev. (1998) [Pubmed]
  9. Transcriptional regulatory region of Brn-2 required for its expression in developing olfactory epithelial cells. Hagino-Yamagishi, K., Saijoh, Y., Yamazaki, Y., Yazaki, K., Hamada, H. Brain Res. Dev. Brain Res. (1998) [Pubmed]
  10. Redox regulation of Brn-2/N-Oct-3 POU domain DNA binding activity and proteolytic formation of N-Oct-5 during melanoma cell nuclear extraction. Smith, A.G., Brightwell, G., Smit, S.E., Parsons, P.G., Sturm, R.A. Melanoma Res. (1998) [Pubmed]
  11. The murine Otp homeobox gene plays an essential role in the specification of neuronal cell lineages in the developing hypothalamus. Wang, W., Lufkin, T. Dev. Biol. (2000) [Pubmed]
  12. POU transcription factors control expression of CNS stem cell-specific genes. Josephson, R., Müller, T., Pickel, J., Okabe, S., Reynolds, K., Turner, P.A., Zimmer, A., McKay, R.D. Development (1998) [Pubmed]
  13. Sim2 contributes to neuroendocrine hormone gene expression in the anterior hypothalamus. Goshu, E., Jin, H., Lovejoy, J., Marion, J.F., Michaud, J.L., Fan, C.M. Mol. Endocrinol. (2004) [Pubmed]
  14. Hox/Pbx and Brn binding sites mediate Pax3 expression in vitro and in vivo. Pruitt, S.C., Bussman, A., Maslov, A.Y., Natoli, T.A., Heinaman, R. Gene Expr. Patterns (2004) [Pubmed]
  15. Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2. Schonemann, M.D., Ryan, A.K., McEvilly, R.J., O'Connell, S.M., Arias, C.A., Kalla, K.A., Li, P., Sawchenko, P.E., Rosenfeld, M.G. Genes Dev. (1995) [Pubmed]
  16. Class III POU genes: generation of homopolymeric amino acid repeats under GC pressure in mammals. Sumiyama, K., Washio-Watanabe, K., Saitou, N., Hayakawa, T., Ueda, S. J. Mol. Evol. (1996) [Pubmed]
  17. Multiple promoter elements differentially regulate the expression of the mouse tenascin gene. Copertino, D.W., Edelman, G.M., Jones, F.S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  18. From embryonal carcinoma cells to neurons: the P19 pathway. Bain, G., Ray, W.J., Yao, M., Gottlieb, D.I. Bioessays (1994) [Pubmed]
  19. Accumulation of manganese in the brain of mice after intravenous injection of manganese-based contrast agents. Gallez, B., Baudelet, C., Adline, J., Geurts, M., Delzenne, N. Chem. Res. Toxicol. (1997) [Pubmed]
  20. The class III POU domain protein Brn-1 can fully replace the related Oct-6 during schwann cell development and myelination. Friedrich, R.P., Schlierf, B., Tamm, E.R., Bösl, M.R., Wegner, M. Mol. Cell. Biol. (2005) [Pubmed]
  21. Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene expression in embryonic and neural stem cells. Catena, R., Tiveron, C., Ronchi, A., Porta, S., Ferri, A., Tatangelo, L., Cavallaro, M., Favaro, R., Ottolenghi, S., Reinbold, R., Schöler, H., Nicolis, S.K. J. Biol. Chem. (2004) [Pubmed]
  22. A POU factor binding site upstream of the Chx10 homeobox gene is required for Chx10 expression in subsets of retinal progenitor cells and bipolar cells. Rowan, S., Cepko, C.L. Dev. Biol. (2005) [Pubmed]
  23. Predominant expression of Brn-2 in the postmitotic neurons of the developing mouse neocortex. Hagino-Yamagishi, K., Saijoh, Y., Ikeda, M., Ichikawa, M., Minamikawa-Tachino, R., Hamada, H. Brain Res. (1997) [Pubmed]
  24. The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse. Nakai, S., Kawano, H., Yudate, T., Nishi, M., Kuno, J., Nagata, A., Jishage, K., Hamada, H., Fujii, H., Kawamura, K. Genes Dev. (1995) [Pubmed]
  25. In vivo labeling of sigma receptors in mouse brain with [3H]4-phenyl-1-(4-phenylbutyl)piperidine. Hashimoto, K., Scheffel, U., London, E.D. Synapse (1995) [Pubmed]
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