Gene Symbol: Pou3f2
Description: POU domain, class 3, transcription factor 2
Alias: 9430075J19Rik, A230098E07Rik, Brn-2, Brn2, OTF-7, Otf7, oct-7, POU domain, class 3, transcription factor 2, brain-2 class III POU-domain protein, brain-specific homeobox/POU domain protein 2, nervous system-specific octamer-binding transcription factor N-Oct-3, octamer-binding protein 7, octamer-binding transcription factor 7
Species: mouse
Products:     Pou3f2

Top Publications

  1. Tanaka S, Kamachi Y, Tanouchi A, Hamada H, Jing N, Kondoh H. Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells. Mol Cell Biol. 2004;24:8834-46 pubmed
    ..Class III POU (Brn2) was expressed at high levels, localizing to the nucleus in the ventricular and subventricular zones; moderate ..
  2. Hoser M, Potzner M, Koch J, Bösl M, Wegner M, Sock E. Sox12 deletion in the mouse reveals nonreciprocal redundancy with the related Sox4 and Sox11 transcription factors. Mol Cell Biol. 2008;28:4675-87 pubmed publisher
    ..Because of differences in expression levels and transactivation rates, however, functional compensation is not reciprocal. ..
  3. Britanova O, de Juan Romero C, Cheung A, Kwan K, Schwark M, Gyorgy A, et al. Satb2 is a postmitotic determinant for upper-layer neuron specification in the neocortex. Neuron. 2008;57:378-92 pubmed publisher
    ..Satb2 therefore is required for the initiation of the UL1-specific genetic program and for the inactivation of DL- and UL2-specific genes. ..
  4. Schonemann M, Ryan A, McEvilly R, O Connell S, Arias C, Kalla K, et al. Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2. Genes Dev. 1995;9:3122-35 pubmed
  5. Sumiyama K, Washio Watanabe K, Saitou N, Hayakawa T, Ueda S. Class III POU genes: generation of homopolymeric amino acid repeats under GC pressure in mammals. J Mol Evol. 1996;43:170-8 pubmed
    ..Those amino acids were encoded by triplet codons with relatively high GC content. These results suggest that the GC pressure has facilitated generation of the homopolymeric amino acid repeats. ..
  6. Miyagi S, Nishimoto M, Saito T, Ninomiya M, Sawamoto K, Okano H, et al. The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon. J Biol Chem. 2006;281:13374-81 pubmed
    ..Our data also suggest that the specific recruitment of these proteins to the SRR2 in the telencephalon defines the spatiotemporal activity of the enhancer in the developing nervous system. ..
  7. Pulvers J, Huttner W. Brca1 is required for embryonic development of the mouse cerebral cortex to normal size by preventing apoptosis of early neural progenitors. Development. 2009;136:1859-68 pubmed publisher
    ..Our results show that Brca1 is required for the cerebral cortex to develop to normal size by preventing the apoptosis of early cortical progenitors and their immediate progeny. ..
  8. Sugitani Y, Nakai S, Minowa O, Nishi M, Jishage K, Kawano H, et al. Brn-1 and Brn-2 share crucial roles in the production and positioning of mouse neocortical neurons. Genes Dev. 2002;16:1760-5 pubmed
    ..These data indicate that Brn-1 and Brn-2 share roles in the production and positioning of neocortical neuron development. ..
  9. Siegenthaler J, Tremper Wells B, Miller M. Foxg1 haploinsufficiency reduces the population of cortical intermediate progenitor cells: effect of increased p21 expression. Cereb Cortex. 2008;18:1865-75 pubmed
    ..mice have thinner neocortices than wild-type controls, specifically in the supragranular layers, as detected by Brn2 immunostaining...

More Information


  1. Jin Z, Liu L, Bian W, Chen Y, Xu G, Cheng L, et al. Different transcription factors regulate nestin gene expression during P19 cell neural differentiation and central nervous system development. J Biol Chem. 2009;284:8160-73 pubmed publisher
    ..Sox2 and SF1 may mediate basal nestin expression in undifferentiated P19EC cells, whereas Sox2, Brn1, and Brn2 bind to the enhancer in P19 neural progenitor cells...
  2. Catena R, Tiveron C, Ronchi A, Porta S, Ferri A, Tatangelo L, et al. Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene expression in embryonic and neural stem cells. J Biol Chem. 2004;279:41846-57 pubmed
    ..Mutation of POU factor binding sites, able to recognize the neural factors Brn1 and Brn2, shows that these sites contribute to transgene activity in neural cells...
  3. Nakai S, Kawano H, Yudate T, Nishi M, Kuno J, Nagata A, et al. The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse. Genes Dev. 1995;9:3109-21 pubmed
    ..These results strongly suggest that Brn-2 plays an essential role in the determination and development of the PVN and SO neuronal lineages in the hypothalamus. ..
  4. Hosoya T, Oda Y, Takahashi S, Morita M, Kawauchi S, Ema M, et al. Defective development of secretory neurones in the hypothalamus of Arnt2-knockout mice. Genes Cells. 2001;6:361-74 pubmed
    ..Consistent with these observations, prospective SON and PVN neurones which express Brn2 appeared around E13...
  5. He X, Treacy M, Simmons D, Ingraham H, Swanson L, Rosenfeld M. Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature. 1989;340:35-41 pubmed
  6. Hara Y, Rovescalli A, Kim Y, Nirenberg M. Structure and evolution of four POU domain genes expressed in mouse brain. Proc Natl Acad Sci U S A. 1992;89:3280-4 pubmed
    ..Additional duplications of the ancestral class III POU domain gene (or mRNA) would create the Brain-1, Brain-2, Brain-4, and Scip genes. ..
  7. Keith B, Adelman D, Simon M. Targeted mutation of the murine arylhydrocarbon receptor nuclear translocator 2 (Arnt2) gene reveals partial redundancy with Arnt. Proc Natl Acad Sci U S A. 2001;98:6692-7 pubmed
    ..5. These results demonstrate that Arnt and Arnt2 have both unique and overlapping essential functions in embryonic development. ..
  8. Michaud J, Rosenquist T, May N, Fan C. Development of neuroendocrine lineages requires the bHLH-PAS transcription factor SIM1. Genes Dev. 1998;12:3264-75 pubmed
    ..these neuronal lineages in the PVN/SON are also missing in mice bearing a mutation in the POU transcription factor BRN2. We provide evidence that, during development of the Sim1 mutant hypothalamus, the prospective PVN/SON region fails ..
  9. McEvilly R, de Diaz M, Schonemann M, Hooshmand F, Rosenfeld M. Transcriptional regulation of cortical neuron migration by POU domain factors. Science. 2002;295:1528-32 pubmed
  10. Castro D, Skowronska Krawczyk D, Armant O, Donaldson I, Parras C, Hunt C, et al. Proneural bHLH and Brn proteins coregulate a neurogenic program through cooperative binding to a conserved DNA motif. Dev Cell. 2006;11:831-44 pubmed
    ..Here, we demonstrate that the proneural protein Mash1 and the POU proteins Brn1 and Brn2 interact on the promoter of the Notch ligand Delta1 and synergistically activate Delta1 transcription, a key step ..
  11. Michaud J, DeRossi C, May N, Holdener B, Fan C. ARNT2 acts as the dimerization partner of SIM1 for the development of the hypothalamus. Mech Dev. 2000;90:253-61 pubmed
    ..Together, these results implicate ARNT2 as the in vivo dimerization partner of SIM1 in controlling the development of these neuroendocrine lineages. ..
  12. Shinmyo Y, Asrafuzzaman Riyadh M, Ahmed G, Bin Naser I, Hossain M, Takebayashi H, et al. Draxin from neocortical neurons controls the guidance of thalamocortical projections into the neocortex. Nat Commun. 2015;6:10232 pubmed publisher
    ..These results suggest that draxin from neocortical neurons controls thalamocortical projections into the neocortex, and that this effect is mediated through the DCC and Neo1 receptors. ..
  13. Rodriguez M, Choi J, Park S, Sockanathan S. Gde2 regulates cortical neuronal identity by controlling the timing of cortical progenitor differentiation. Development. 2012;139:3870-9 pubmed
  14. Wang S, Celic I, Choi S, Riccomagno M, Wang Q, Sun L, et al. Dlg5 regulates dendritic spine formation and synaptogenesis by controlling subcellular N-cadherin localization. J Neurosci. 2014;34:12745-61 pubmed publisher
    ..DLG5 regulates synaptogenesis by enhancing the cell surface localization of N-cadherin, revealing a key molecular mechanism for regulating the subcellular localization of this cell adhesion molecule during synaptogenesis. ..
  15. Glasgow S, Carlson J, Zhu W, Chaboub L, Kang P, Lee H, et al. Glia-specific enhancers and chromatin structure regulate NFIA expression and glioma tumorigenesis. Nat Neurosci. 2017;20:1520-1528 pubmed publisher
    ..Complementary genetic studies found that Sox9-Brn2 and Isl1-Lhx3 regulate enhancer activity and NFIA expression in glial and neuronal populations...
  16. Machon O, Backman M, Machonova O, Kozmik Z, Vacik T, Andersen L, et al. A dynamic gradient of Wnt signaling controls initiation of neurogenesis in the mammalian cortex and cellular specification in the hippocampus. Dev Biol. 2007;311:223-37 pubmed
    ..This suggests that the dose of canonical Wnt signaling determines cellular fate in the developing cortex and hippocampus, and that recession of Wnt signaling acts as a morphogenetic gradient regulating neurogenesis in the cortex. ..
  17. Lee Y, Katyal S, Downing S, Zhao J, Russell H, McKinnon P. Neurogenesis requires TopBP1 to prevent catastrophic replicative DNA damage in early progenitors. Nat Neurosci. 2012;15:819-26 pubmed publisher
    ..Thus, TopBP1 is crucial for maintaining genome integrity in the early progenitors that drive neurogenesis. ..
  18. Kim D, Matsuda T, Cepko C. A core paired-type and POU homeodomain-containing transcription factor program drives retinal bipolar cell gene expression. J Neurosci. 2008;28:7748-64 pubmed publisher
    ..The paired-type homeodomain transcription factors (TFs) Crx and Otx2 and the POU homeodomain factor Brn2 are expressed in bipolar cells and interacted with the predicted binding sequences as assessed by electrophoretic ..
  19. Bormuth I, Yan K, Yonemasu T, Gummert M, Zhang M, Wichert S, et al. Neuronal basic helix-loop-helix proteins Neurod2/6 regulate cortical commissure formation before midline interactions. J Neurosci. 2013;33:641-51 pubmed publisher
    ..Our findings define a new stage in corpus callosum development and demonstrate that neocortical projection neurons require transcriptional specification by neuronal bHLH proteins to execute an intrinsic program of remote connectivity. ..
  20. Xie Y, Jüschke C, Esk C, Hirotsune S, Knoblich J. The phosphatase PP4c controls spindle orientation to maintain proliferative symmetric divisions in the developing neocortex. Neuron. 2013;79:254-65 pubmed publisher
    ..Our results identify a key regulator of cortical development and demonstrate that changes in the orientation of progenitor division are responsible for the transition between symmetric and asymmetric cell division. ..
  21. Shimada M, Dumitrache L, Russell H, McKinnon P. Polynucleotide kinase-phosphatase enables neurogenesis via multiple DNA repair pathways to maintain genome stability. EMBO J. 2015;34:2465-80 pubmed publisher
    ..These data illuminate the basis for selective neural vulnerability in DNA repair deficiency disease. ..
  22. Acampora D, Postiglione M, Avantaggiato V, Di Bonito M, Vaccarino F, Michaud J, et al. Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene. Genes Dev. 1999;13:2787-800 pubmed
    ..that directs terminal differentiation of the PVN, SON, and aPV, act in parallel and are both required to maintain Brn2 expression which, in turn, is required for neuronal cell lineages secreting oxytocin (OT), arginine vasopressin (..
  23. Pinner S, Jordan P, Sharrock K, Bazley L, Collinson L, Marais R, et al. Intravital imaging reveals transient changes in pigment production and Brn2 expression during metastatic melanoma dissemination. Cancer Res. 2009;69:7969-77 pubmed publisher
    ..A subpopulation of cells containing little or no pigment and high levels of Brn2::GFP expression are motile in the primary tumor and enter the vasculature...
  24. Ellmann L, Joshi M, Resink T, Bosserhoff A, Kuphal S. BRN2 is a transcriptional repressor of CDH13 (T-cadherin) in melanoma cells. Lab Invest. 2012;92:1788-800 pubmed publisher
    ..Bioinformatical analysis pointed to the presence of known BRN2 (also known as POU3F2 and N-Oct-3)-binding motifs in the CDH13 promoter sequence...
  25. Gompers A, Su Feher L, Ellegood J, Copping N, Riyadh M, Stradleigh T, et al. Germline Chd8 haploinsufficiency alters brain development in mouse. Nat Neurosci. 2017;20:1062-1073 pubmed publisher
    ..This integrative analysis offers an initial picture of the consequences of Chd8 haploinsufficiency for brain development. ..
  26. Nasu M, Yada S, Igarashi A, Sutoo D, Akiyama K, Ito M, et al. Mammalian-specific sequences in pou3f2 contribute to maternal behavior. Genome Biol Evol. 2014;6:1145-56 pubmed publisher
    ..mammalian maternal behavior, pup retrieval, in nonmammalized mice, in which the transcription factor Pou3f2 was replaced with the Xenopus ortholog lacking all of the homopolymeric amino acid repeats of mammalian POU3F2...
  27. Wang P, Chou F, Ramachandran S, Xia S, Chen H, Guo F, et al. Crucial roles of the Arp2/3 complex during mammalian corticogenesis. Development. 2016;143:2741-52 pubmed publisher
    ..Our data suggest that Arp2/3-mediated actin assembly might be particularly important for neuronal cell motility in a soft or poorly adhesive matrix environment. ..
  28. Cheung A, Kondo S, Abdel Mannan O, Chodroff R, Sirey T, Bluy L, et al. The subventricular zone is the developmental milestone of a 6-layered neocortex: comparisons in metatherian and eutherian mammals. Cereb Cortex. 2010;20:1071-81 pubmed publisher
    ..divisions in the ventricular zone (VZ) were similar in all species, with comparable mRNA expression patterns of Brn2, Cux2, NeuroD6, Tbr2, and Pax6 in opossum (P12 and P20) and mouse (embryonic day 15 and P0)...
  29. Malik K, Jaffe H, Brady J, Young W. The class III POU factor Brn-4 interacts with other class III POU factors and the heterogeneous nuclear ribonucleoprotein U. Brain Res Mol Brain Res. 1997;45:99-107 pubmed
    ..This result suggests another mechanism by which a POU protein can influence gene expression: by facilitating the processing of pre-mRNA whose transcription it has stimulated. ..
  30. Hagino Yamagishi K, Saijoh Y, Ikeda M, Ichikawa M, Minamikawa Tachino R, Hamada H. Predominant expression of Brn-2 in the postmitotic neurons of the developing mouse neocortex. Brain Res. 1997;752:261-8 pubmed
    ..Therefore, this transcription factor may be involved in the migration and/or maturation process of the immature neuronal cells. ..
  31. Lee F, Fadel M, Preston Maher K, Cordes S, Clapcote S, Price D, et al. Disc1 point mutations in mice affect development of the cerebral cortex. J Neurosci. 2011;31:3197-206 pubmed publisher
    ..Overall, the histology of Disc1 mutant mouse cortex is reminiscent of the findings in schizophrenia. These results provide further evidence that Disc1 participates in cortical development, including neurogenesis and neuron migration. ..
  32. Huang Y, Iwamoto K, Kurosaki T, Nasu M, Ueda S. The neuronal POU transcription factor Brn-2 interacts with Jab1, a gene involved in the onset of neurodegenerative diseases. Neurosci Lett. 2005;382:175-8 pubmed
  33. Molyneaux B, Arlotta P, Hirata T, Hibi M, Macklis J. Fezl is required for the birth and specification of corticospinal motor neurons. Neuron. 2005;47:817-31 pubmed
  34. Seto Y, Ishiwata S, Hoshino M. Characterization of Olig2 expression during cerebellar development. Gene Expr Patterns. 2014;15:1-7 pubmed publisher
    ..This expression pattern suggests that Olig2 may have an important role in the early stage of Purkinje cell development. ..
  35. Lodato M, Ng C, Wamstad J, Cheng A, Thai K, Fraenkel E, et al. SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state. PLoS Genet. 2013;9:e1003288 pubmed publisher
    ..We found that, similar to its association with OCT4 (Pou5f1) in ESCs, the related POU family member BRN2 (Pou3f2) co-occupied a large set of putative distal enhancers with SOX2 in NPCs...
  36. Goshu E, Jin H, Lovejoy J, Marion J, Michaud J, Fan C. Sim2 contributes to neuroendocrine hormone gene expression in the anterior hypothalamus. Mol Endocrinol. 2004;18:1251-62 pubmed
    ..One of their common downstream genes, Brn2, is necessary for oxytocin, vasopressin, and CRH cell differentiation...
  37. Hashizume K, Yamanaka M, Ueda S. POU3F2 participates in cognitive function and adult hippocampal neurogenesis via mammalian-characteristic amino acid repeats. Genes Brain Behav. 2018;17:118-125 pubmed publisher
    b>POU3F2/BRN-2 is a transcription factor that is mainly expressed in the central nervous system and plays an important role in brain development...
  38. Hsu L, Nam S, Cui Y, Chang C, Wang C, Kuo H, et al. Lhx2 regulates the timing of β-catenin-dependent cortical neurogenesis. Proc Natl Acad Sci U S A. 2015;112:12199-204 pubmed publisher
    ..Thus, we concluded that Lhx2 is required for β-catenin function in maintaining cortical progenitor proliferation and controls the timing of cortical neurogenesis. ..
  39. Parthasarathy S, Srivatsa S, Nityanandam A, Tarabykin V. Ntf3 acts downstream of Sip1 in cortical postmitotic neurons to control progenitor cell fate through feedback signaling. Development. 2014;141:3324-30 pubmed publisher
    ..Loss of Ntf3, by contrast, causes an increase in layer VI neurons but does not rescue the Sip1 mutant phenotype, implying that other parallel pathways also control the timing of progenitor cell fate switch. ..
  40. Yano M, Hayakawa Yano Y, Mele A, Darnell R. Nova2 regulates neuronal migration through an RNA switch in disabled-1 signaling. Neuron. 2010;66:848-58 pubmed publisher
    ..Thus, Nova2 regulates an RNA switch controlling the ability of Dab1 to mediate neuronal responsiveness to reelin signaling and neuronal migration, suggesting new links between splicing regulation, brain disease, and development. ..
  41. Urban S, Kobi D, Ennen M, Langer D, Le Gras S, Ye T, et al. A Brn2-Zic1 axis specifies the neuronal fate of retinoic-acid-treated embryonic stem cells. J Cell Sci. 2015;128:2303-18 pubmed publisher
    ..Here, we show that the transcription factor Brn2 (also known as Pou3f2) is essential for the neuronal differentiation programme...
  42. Goodall J, Wellbrock C, Dexter T, Roberts K, Marais R, Goding C. The Brn-2 transcription factor links activated BRAF to melanoma proliferation. Mol Cell Biol. 2004;24:2923-31 pubmed
    ..The results suggest that the high levels of Brn-2 expression observed in melanomas link BRAF signaling to increased proliferation. ..
  43. Enriquez Rios V, Dumitrache L, Downing S, Li Y, Brown E, Russell H, et al. DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis. J Neurosci. 2017;37:893-905 pubmed publisher
    ..These data demonstrate functionally distinct, but cooperative, roles for each kinase in preserving genome stability in the nervous system. ..
  44. Li P, Fu X, Smith N, Ziobro J, Curiel J, Tenga M, et al. Loss of CLOCK Results in Dysfunction of Brain Circuits Underlying Focal Epilepsy. Neuron. 2017;96:387-401.e6 pubmed publisher
    ..Altogether, these data show that disruption of CLOCK alters cortical circuits and may lead to generation of focal epilepsy. ..
  45. Iwafuchi Doi M, Matsuda K, Murakami K, Niwa H, Tesar P, Aruga J, et al. Transcriptional regulatory networks in epiblast cells and during anterior neural plate development as modeled in epiblast stem cells. Development. 2012;139:3926-37 pubmed publisher
    ..The direct interaction of these factors with enhancers of Otx2, Hesx1 and Sox2 genes was demonstrated. Thus, a combination of regulatory processes that suppresses non-ANP lineages and promotes neural plate development determines the ANP...
  46. Hoeck J, Jandke A, Blake S, Nye E, Spencer Dene B, Brandner S, et al. Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun. Nat Neurosci. 2010;13:1365-72 pubmed publisher
    ..Thus Fbw7 controls neurogenesis by antagonizing Notch and c-Jun N-terminal kinase (JNK)/c-Jun signaling. ..
  47. Wapinski O, Vierbuchen T, Qu K, Lee Q, Chanda S, Fuentes D, et al. Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons. Cell. 2013;155:621-35 pubmed publisher
    ..the direct conversion of fibroblasts into induced neuronal (iN) cells mediated by the transcription factors Ascl1, Brn2, and Myt1l...
  48. Alsiö J, Tarchini B, Cayouette M, Livesey F. Ikaros promotes early-born neuronal fates in the cerebral cortex. Proc Natl Acad Sci U S A. 2013;110:E716-25 pubmed publisher
    ..These data suggest that Ikaros plays a similar role in regulating early temporal fates in the mammalian cerebral cortex as Ikaros/Hunchback proteins do in the Drosophila nerve cord. ..
  49. Tan X, Fan X, Kim H, Butler R, Webb P, Warner M, et al. Liver X receptor beta and thyroid hormone receptor alpha in brain cortical layering. Proc Natl Acad Sci U S A. 2010;107:12305-10 pubmed publisher
  50. Caqueret A, Boucher F, Michaud J. Laminar organization of the early developing anterior hypothalamus. Dev Biol. 2006;298:95-106 pubmed
    ..In addition, our analysis suggests that Sim1 function is required for the production or the survival of postmitotic neurons as well as for correct positioning of AH neurons...
  51. Nomura T, Takahashi M, Hara Y, Osumi N. Patterns of neurogenesis and amplitude of Reelin expression are essential for making a mammalian-type cortex. PLoS ONE. 2008;3:e1454 pubmed publisher
    ..These lines of evidence shed light on the developmental programs underlying the evolution of the mammalian specific laminated cortex...
  52. Chee M, Jo S, Sohn K, Kim C, Lee J, Lee Y. Effects of Brn2 overexpression on eccrine sweat gland development in the mouse paw. Biochem Biophys Res Commun. 2017;490:901-905 pubmed publisher
    ..In mice, eccrine sweat glands are present only in the paw pad. Brn2 is a protein belonging to a large family of transcription factors...
  53. Konno D, Iwashita M, Satoh Y, Momiyama A, Abe T, Kiyonari H, et al. The mammalian DM domain transcription factor Dmrta2 is required for early embryonic development of the cerebral cortex. PLoS ONE. 2012;7:e46577 pubmed publisher