pou domain factors


Summary: A family of transcription factors characterized by the presence of a bipartite DNA-binding domain known as the POU domain. The POU domain contains two subdomains, a POU-specific domain and a POU-homeodomain. The POU domain was originally identified as a region of approximately 150 amino acids shared between the Pit-1, Oct-1, Oct-2, and Unc-86 transcription factors.

Top Publications

  1. Pang Z, Yang N, Vierbuchen T, Ostermeier A, Fuentes D, Yang T, et al. Induction of human neuronal cells by defined transcription factors. Nature. 2011;476:220-3 pubmed publisher
    ..These methods may facilitate robust generation of patient-specific human neurons for in vitro disease modelling or future applications in regenerative medicine. ..
  2. Heydemann A, Nguyen L, Crenshaw E. Regulatory regions from the Brn4 promoter direct LACZ expression to the developing forebrain and neural tube. Brain Res Dev Brain Res. 2001;128:83-90 pubmed
    ..These data characterize a transgenic promoter region that will be useful in directing expression to the developing neural tube during the ontogeny of the forebrain. ..
  3. Lee M, Salvaterra P. Abnormal chemosensory jump 6 is a positive transcriptional regulator of the cholinergic gene locus in Drosophila olfactory neurons. J Neurosci. 2002;22:5291-9 pubmed
  4. de Celis J, Llimargas M, Casanova J. Ventral veinless, the gene encoding the Cf1a transcription factor, links positional information and cell differentiation during embryonic and imaginal development in Drosophila melanogaster. Development. 1995;121:3405-16 pubmed
    ..We propose that the gene vvl integrates information from different signalling molecules and regulates the expression of specific cell differentiation genes during tracheal development and vein differentiation. ..
  5. Naranjo S, Voesenek K, de la Calle Mustienes E, Robert Moreno A, Kokotas H, Grigoriadou M, et al. Multiple enhancers located in a 1-Mb region upstream of POU3F4 promote expression during inner ear development and may be required for hearing. Hum Genet. 2010;128:411-9 pubmed publisher
    ..In addition, the novel deletion demonstrates that the previous reported enhancer, although not sufficient, is essential for POU3F4 function during inner ear development. ..
  6. Iwafuchi Doi M, Yoshida Y, Onichtchouk D, Leichsenring M, Driever W, Takemoto T, et al. The Pou5f1/Pou3f-dependent but SoxB-independent regulation of conserved enhancer N2 initiates Sox2 expression during epiblast to neural plate stages in vertebrates. Dev Biol. 2011;352:354-66 pubmed publisher
    ..In contrast, the enhancer N2-mediated, POU factor-dependent activation of Sox2, without involvement of Sox2, is a phylogenetically conserved core mechanism that functions in gene regulatory networks at early embryonic stages...
  7. Marlin S, Moizard M, David A, Chaissang N, Raynaud M, Jonard L, et al. Phenotype and genotype in females with POU3F4 mutations. Clin Genet. 2009;76:558-63 pubmed publisher
    ..The phenotype of eight independent females carrying POU3F4 anomalies is defined, and a late-onset hearing loss is found in three patients. Only one has an inner ear malformation. No genotype/phenotype correlation is identified. ..
  8. Samadi D, Saunders J, Crenshaw E. Mutation of the POU-domain gene Brn4/Pou3f4 affects middle-ear sound conduction in the mouse. Hear Res. 2005;199:11-21 pubmed
  9. Stankovic K, Hennessey A, Herrmann B, Mankarious L. Cochlear implantation in children with congenital X-linked deafness due to novel mutations in POU3F4 gene. Ann Otol Rhinol Laryngol. 2010;119:815-22 pubmed
    ..Limited auditory perception and language acquisition may result. Amplification may sometimes be a better alternative than cochlear implantation, despite the severity of the hearing loss. ..

More Information


  1. Certel S, Thor S. Specification of Drosophila motoneuron identity by the combinatorial action of POU and LIM-HD factors. Development. 2004;131:5429-39 pubmed
    ..These results suggest that in the TN motoneuron context, Islet and Lim3 may specify axon target selection through the actions of IgSF call-adhesion molecules. ..
  2. Anderson M, Certel S, Certel K, Lee T, Montell D, Johnson W. Function of the Drosophila POU domain transcription factor drifter as an upstream regulator of breathless receptor tyrosine kinase expression in developing trachea. Development. 1996;122:4169-78 pubmed
    ..This example of a mechanism for maintenance of a committed cell fate offers a model for understanding how essential gene activities can be maintained throughout organogenesis. ..
  3. 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
    ..Our results strongly indicate that SIM1 functions upstream to maintain Brn2 expression, which in turn directs the terminal differentiation of specific neuroendocrine lineages within the PVN/SON. ..
  4. Cifuentes F, Garcia Bellido A. Proximo-distal specification in the wing disc of Drosophila by the nubbin gene. Proc Natl Acad Sci U S A. 1997;94:11405-10 pubmed
    ..We discuss the role of nub in the wing's proximo-distal axis and in the formation of compartment boundaries. ..
  5. 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
    ..Evidence also suggests that such interactions are involved in the regulation of neural primordial cells. ..
  6. Chi Y, Frantz J, Oh B, Hansen L, Dhe Paganon S, Shoelson S. Diabetes mutations delineate an atypical POU domain in HNF-1alpha. Mol Cell. 2002;10:1129-37 pubmed
    ..The numerous diabetes-causing mutations in HNF-1alpha thus identified a previously unrecognized POU domain which was used as a search model to identify additional POU domain proteins in sequence databases. ..
  7. Komiyama T, Johnson W, Luo L, Jefferis G. From lineage to wiring specificity. POU domain transcription factors control precise connections of Drosophila olfactory projection neurons. Cell. 2003;112:157-67 pubmed
    ..Acj6 also controls stereotypical axon terminal arborization of PNs in a central target, suggesting that the connectivity of PN axons and dendrites in different brain centers is coordinately regulated. ..
  8. Zhang T, Kang L, Zhang Z, Xu W. Identification of a POU factor involved in regulating the neuron-specific expression of the gene encoding diapause hormone and pheromone biosynthesis-activating neuropeptide in Bombyx mori. Biochem J. 2004;380:255-63 pubmed publisher
    ..POU-M1 was found to exhibit the same transcriptional activities as POU-M2. Taken together, these results demonstrate that POU-M2 plays an important role in the transcriptional regulation of the Bom-DH-PBAN gene...
  9. Goodall J, Carreira S, Denat L, Kobi D, Davidson I, Nuciforo P, et al. Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells. Cancer Res. 2008;68:7788-94 pubmed publisher
    ..Remarkably, in melanoma biopsies, Mitf and Brn-2 each mark a distinct subpopulation of melanoma cells, providing a striking illustration of melanoma tumor heterogeneity with implications for melanoma therapy. ..
  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
    ..We thus propose that Mash1 synergizes with Brn factors to regulate multiple steps of neurogenesis. ..
  11. Ahn K, Passero F, Crenshaw E. Otic mesenchyme expression of Cre recombinase directed by the inner ear enhancer of the Brn4/Pou3f4 gene. Genesis. 2009;47:137-41 pubmed publisher
    ..Thus, this Cre pedigree can induce conditional rearrangement of genes in the otic mesenchyme, and will serve as a powerful genetic tool to characterize the function of genes in the mesenchymal tissues of the inner ear. ..
  12. Cao Y, Siegel D, Oswald F, Knöchel W. Oct25 represses transcription of nodal/activin target genes by interaction with signal transducers during Xenopus gastrulation. J Biol Chem. 2008;283:34168-77 pubmed publisher
    ..Our results provide a novel view in that Oct25 controls the nodal/activin pathway and thus maintains the undifferentiated state of embryonic cells in preventing them from premature differentiation. ..
  13. Braunstein E, Crenshaw E, Morrow B, Adams J. Cooperative function of Tbx1 and Brn4 in the periotic mesenchyme is necessary for cochlea formation. J Assoc Res Otolaryngol. 2008;9:33-43 pubmed publisher
  14. Phippard D, Boyd Y, Reed V, Fisher G, Masson W, Evans E, et al. The sex-linked fidget mutation abolishes Brn4/Pou3f4 gene expression in the embryonic inner ear. Hum Mol Genet. 2000;9:79-85 pubmed
    ..Finally, these results demonstrate that the slf mutation is a good mouse model for the most prevalent form of X-linked congenital deafness in man, which is associated with mutations in the human Brn4 ortholog, POU3F4. ..
  15. Le Moine C, Young W. RHS2, a POU domain-containing gene, and its expression in developing and adult rat. Proc Natl Acad Sci U S A. 1992;89:3285-9 pubmed
    ..Expression of RHS2 in the caudate putamen was increased by elimination of its nigrostriatal dopaminergic innervation. ..
  16. Kuhlbrodt K, Herbarth B, Sock E, Enderich J, Hermans Borgmeyer I, Wegner M. Cooperative function of POU proteins and SOX proteins in glial cells. J Biol Chem. 1998;273:16050-7 pubmed
    ..Our data suggest the existence of a specific code in which POU proteins require specific Sox proteins to exhibit cooperative effects in glial cells. ..
  17. Bitner Glindzicz M, Turnpenny P, Hoglund P, Kaariainen H, Sankila E, van der Maarel S, et al. Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3. Hum Mol Genet. 1995;4:1467-9 pubmed
  18. Thomson J, Murphy K, Baker E, Sutherland G, Parsons P, Sturm R, et al. The brn-2 gene regulates the melanocytic phenotype and tumorigenic potential of human melanoma cells. Oncogene. 1995;11:691-700 pubmed
    ..These results suggest roles for brn-2 in the determination of the melanocytic lineage and in the tumorigenic phenotype of melanoma. ..
  19. Kitamoto T, Salvaterra P. A POU homeo domain protein related to dPOU-19/pdm-1 binds to the regulatory DNA necessary for vital expression of the Drosophila choline acetyltransferase gene. J Neurosci. 1995;15:3509-18 pubmed
    ..We propose that vital expression of the Drosophila ChAT gene is regulated by a member of the dPOU-19/pdm-1 putative transcription factor family. ..
  20. Yeo S, Lloyd A, Kozak K, Dinh A, Dick T, Yang X, et al. On the functional overlap between two Drosophila POU homeo domain genes and the cell fate specification of a CNS neural precursor. Genes Dev. 1995;9:1223-36 pubmed
    ..Hence, the failure of the POU mutants to produce mature RP2 neurons is not attributable to a block in GMC4-2a cell division per se but, rather, because the GMC4-2a cells fail to acquire their correct cellular identity. ..
  21. Zelzer E, Shilo B. Interaction between the bHLH-PAS protein Trachealess and the POU-domain protein Drifter, specifies tracheal cell fates. Mech Dev. 2000;91:163-73 pubmed
    ..A direct interaction between Drifter and Trh proteins, mediated by the PAS domain of Trh and the POU domain of Drifter, was demonstrated. ..
  22. Ghislain J, Charnay P. Control of myelination in Schwann cells: a Krox20 cis-regulatory element integrates Oct6, Brn2 and Sox10 activities. EMBO Rep. 2006;7:52-8 pubmed
  23. Larroux C, Luke G, Koopman P, Rokhsar D, Shimeld S, Degnan B. Genesis and expansion of metazoan transcription factor gene classes. Mol Biol Evol. 2008;25:980-96 pubmed publisher
    ..Transcription factor orthologues present in sponge, cnidarian, and bilaterian genomes may represent part of the core metazoan regulatory network underlying the origin of animal development and multicellularity. ..
  24. Cook A, Sturm R. POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis. Pigment Cell Melanoma Res. 2008;21:611-26 pubmed publisher
    ..Recent studies have shown BRN2 to be responsive to MAPK pathway activation and to modulate the levels of MITF so as to suppress the differentiated melanocytic phenotype and to enhance tumour metastasis. ..
  25. Herr W, Cleary M. The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes Dev. 1995;9:1679-93 pubmed
  26. Junell A, Uvell H, Pick L, Engstrom Y. Isolation of regulators of Drosophila immune defense genes by a double interaction screen in yeast. Insect Biochem Mol Biol. 2007;37:202-12 pubmed
    ..The importance of POU proteins in development and differentiation in Drosophila and mammals is well documented, but their role in regulation of Drosophila immune defense genes is a new and essential finding. ..
  27. Wang Q, Li Q, Rao S, Zhao Y, Yuan H, Yang W, et al. A novel mutation of POU3F4 causes congenital profound sensorineural hearing loss in a large Chinese family. Laryngoscope. 2006;116:944-50 pubmed
    ..Our findings provided confirmatory molecular evidence to support that development of congenital profound sensorineural hearing loss in the Chinese population results from a novel mutation in the same gene. ..
  28. Junell A, Uvell H, Davis M, Edlundh Rose E, Antonsson A, Pick L, et al. The POU transcription factor Drifter/Ventral veinless regulates expression of Drosophila immune defense genes. Mol Cell Biol. 2010;30:3672-84 pubmed publisher
  29. Vore A, Chang E, Hoppe J, Butler M, Forrester S, Schneider M, et al. Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness. Arch Otolaryngol Head Neck Surg. 2005;131:1057-63 pubmed
    ..Affected males can also present with vestibular dysfunction that is associated with delayed developmental motor milestones. Intrafamilial variability occurs. ..
  30. Rowan S, Cepko C. 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. Dev Biol. 2005;281:240-55 pubmed
    ..and biochemical analysis, a key binding site in this enhancer was found and was shown to be bound by the POU domain factors, Brn-2 and Tst-1/SCIP, in retinal extracts...
  31. Okamoto K, Wakamiya M, Noji S, Koyama E, Taniguchi S, Takemura R, et al. A novel class of murine POU gene predominantly expressed in central nervous system. J Biol Chem. 1993;268:7449-57 pubmed
    ..Emb mRNA expressed in testis, on the other hand, encodes a smaller protein lacking most of the amino-terminal region. ..
  32. Certel K, Anderson M, Shrigley R, Johnson W. Distinct variant DNA-binding sites determine cell-specific autoregulated expression of the Drosophila POU domain transcription factor drifter in midline glia or trachea. Mol Cell Biol. 1996;16:1813-23 pubmed
  33. Heller R, Stoffers D, Liu A, Schedl A, Crenshaw E, Madsen O, et al. The role of Brn4/Pou3f4 and Pax6 in forming the pancreatic glucagon cell identity. Dev Biol. 2004;268:123-34 pubmed
    ..2 cells. The pancreatic phenotype of the pax6 mutants can be rescued with a YAC clone containing the human Pax6 gene. ..
  34. de Kok Y, Cremers C, Ropers H, Cremers F. The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation. Hum Mutat. 1997;10:207-11 pubmed
    ..Since these domains constitute only 35% of the open reading frame of POU3F4, there is a statistically significant preference for mutations in the POU-specific and POU homeodomain. ..
  35. Cook A, Donatien P, Smith A, Murphy M, Jones M, Herlyn M, et al. Human melanoblasts in culture: expression of BRN2 and synergistic regulation by fibroblast growth factor-2, stem cell factor, and endothelin-3. J Invest Dermatol. 2003;121:1150-9 pubmed
    ..These finding implicate BRN2 as an early marker of melanoblasts that may contribute to the hierarchy of melanocytic gene control. ..
  36. Nakanishi N, Yuan D, Hartenstein V, Jacobs D. Evolutionary origin of rhopalia: insights from cellular-level analyses of Otx and POU expression patterns in the developing rhopalial nervous system. Evol Dev. 2010;12:404-15 pubmed publisher
    ..This implies some commonality of developmental genetic functions involving these genes in the still poorly constrained common ancestor of bilaterians and cnidarians. ..
  37. Minowa O, Ikeda K, Sugitani Y, Oshima T, Nakai S, Katori Y, et al. Altered cochlear fibrocytes in a mouse model of DFN3 nonsyndromic deafness. Science. 1999;285:1408-11 pubmed
    ..The findings suggest that these fibrocytes, which are mesenchymal in origin and for which a role in potassium ion homeostasis has been postulated, may play a critical role in auditory function...
  38. Li J, Cheng J, Lu Y, Lu Y, Chen A, Sun Y, et al. Identification of a novel mutation in POU3F4 for prenatal diagnosis in a Chinese family with X-linked nonsyndromic hearing loss. J Genet Genomics. 2010;37:787-93 pubmed publisher
    ..647G?A mutation in DNA extracted from the amniotic fluid surrounding the fetus. The appropriate use of genetic testing and prenatal diagnosis plays a key role in reducing the recurrence of genetic defects in high-risk families. ..
  39. Mathis J, Simmons D, He X, Swanson L, Rosenfeld M. Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression. EMBO J. 1992;11:2551-61 pubmed
  40. CHAO C, Loomis Z, Lee J, Sussel L. Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cells. Dev Biol. 2007;312:523-32 pubmed
    ..Furthermore, this study reveals a previously unappreciated early function of NeuroD1 in regulating the specification of alpha, PP and epsilon cells. ..
  41. Holland P, Booth H, Bruford E. Classification and nomenclature of all human homeobox genes. BMC Biol. 2007;5:47 pubmed
    ..The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass. ..
  42. Sze J, Ruvkun G. Activity of the Caenorhabditis elegans UNC-86 POU transcription factor modulates olfactory sensitivity. Proc Natl Acad Sci U S A. 2003;100:9560-5 pubmed
  43. 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. ..
  44. Imafuku I, Waragai M, Takeuchi S, Kanazawa I, Kawabata M, Mouradian M, et al. Polar amino acid-rich sequences bind to polyglutamine tracts. Biochem Biophys Res Commun. 1998;253:16-20 pubmed
    ..Three of these clones could form polar helical structures. These observations suggest that polar amino acid-rich sequences are essential for binding to the polyglutamine tract. ..
  45. Li P, He X, Gerrero M, Mok M, Aggarwal A, Rosenfeld M. Spacing and orientation of bipartite DNA-binding motifs as potential functional determinants for POU domain factors. Genes Dev. 1993;7:2483-96 pubmed
    ..Studies of two classes of neuron-specific POU domain factors (III and IV) indicate that functional specificity on their native response elements is achieved by ..
  46. Bhat K, Poole S, Schedl P. The miti-mere and pdm1 genes collaborate during specification of the RP2/sib lineage in Drosophila neurogenesis. Mol Cell Biol. 1995;15:4052-63 pubmed
    ..Our results indicate that both genes are required for the normal development of this lineage and that the two collaborate during the specification of GMC-1 identity. ..
  47. Tichy A, Ray A, Carlson J. A new Drosophila POU gene, pdm3, acts in odor receptor expression and axon targeting of olfactory neurons. J Neurosci. 2008;28:7121-9 pubmed publisher
    ..Thus, this mutational analysis, the first for a POU class VI gene, demonstrates a role for pdm3 in both of the processes that define the functional organization of ORNs in the olfactory system. ..
  48. Peden E, Kimberly E, Gengyo Ando K, Mitani S, Xue D. Control of sex-specific apoptosis in C. elegans by the BarH homeodomain protein CEH-30 and the transcriptional repressor UNC-37/Groucho. Genes Dev. 2007;21:3195-207 pubmed
  49. Cupit P, Lennard M, Hikima J, Warr G, Cunningham C. Characterization of two POU transcription factor family members from the urochordate Oikopleura dioica. Gene. 2006;383:1-11 pubmed
    ..It is concluded that Oct transcription factors capable of functioning in a similar fashion to vertebrate Oct1/2 were present at the phylogenetic level of the urochordates...
  50. Song M, Lee H, Choi J, Kim S, Bok J, Kim U. Clinical evaluation of DFN3 patients with deletions in the POU3F4 locus and detection of carrier female using MLPA. Clin Genet. 2010;78:524-32 pubmed publisher
  51. 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. ..
  52. Phippard D, Lu L, Lee D, Saunders J, Crenshaw E. Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear. J Neurosci. 1999;19:5980-9 pubmed
    ..On the basis of these data, we suggest that Brn-4 enhances the survival of mesodermal cells during the mesenchymal remodeling that forms the mature bony labyrinth and regulates inductive signaling mechanisms in the otic mesenchyme. ..
  53. Pfisterer U, Kirkeby A, Torper O, Wood J, Nelander J, Dufour A, et al. Direct conversion of human fibroblasts to dopaminergic neurons. Proc Natl Acad Sci U S A. 2011;108:10343-8 pubmed publisher
    ..Such subtype-specific induced neurons derived from human somatic cells could be valuable for disease modeling and cell replacement therapy. ..