Disease relevance of Pou3f2

• The neuronal POU transcription factor Brn-2 interacts with Jab1, a gene involved in the onset of neurodegenerative diseases [1].
• Considering the involvement of Jab1 in the onset of the neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, the interaction between Brn-2 and Jab1 may provide some insights into the understanding of neuronal development and neurodegenerative diseases [1].
• Expression of two of these, Pou3f2 and Gtl3, was reduced both in cells derived from primary tumors and those isolated from metastases [2].
• The POU domain transcription factor Brn-2 has been implicated in control of proliferation and melanoma survival, and its expression is strongly upregulated in melanoma [3].
• 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 [4].

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

• The involvement of Otp and Sim1 in specifying specific hypothalamic neurosecretory cell lineages is shown to operate via distinct signaling pathways that partially overlap with Brn2 [11].
• We obtained Jun-activation-domain-binding protein 1 (Jab1) as a new Brn-2 binding protein [1].
• A hybrid POU/Pbx binding site is recognized in vitro by Pbx-1, Brn-1 and Brn-2 [12].
• One of their common downstream genes, Brn2, is necessary for oxytocin, vasopressin, and CRH cell differentiation [13].
• Two of the four DNA sequence elements are shown to interact with the neural specific Pou-domain class III transcription factors Brn1 and Brn2 [14].

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

• Although the closely related POU domain protein Brn-2 is coexpressed with Oct-6 in Schwann cells, its loss has only mild consequences [20].

Other interactions of Pou3f2

• Direct interaction between Brn-2 and Jab1 was confirmed by using a surface plasmon resonance biosensor [1].
• 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 [21].
• Analysis of the Brn-2 expression pattern shows that it is expressed in intermediate and late RPCs, but not early RPCs, and thus partially overlaps with expression of the reporter activated by the defined Chx10 enhancer [22].
• 5. From E11.5 to postnatal day (P) 0, a high level of Brn-2 expression was observed in the subventricular zone, the intermediate zone, and the outer layer of the neocortex, but not in the ventricular zone [23].
• Transcriptional regulatory region of Brn-2 required for its expression in developing olfactory epithelial cells [9].

Analytical, diagnostic and therapeutic context of Pou3f2

• We generated mice carrying a loss-of-function mutation in Brn-2, a gene encoding a nervous system specific POU transcription factor, by gene targeting in embryonic stem cells [24].
• The regional distribution of radioactivity in the brain 2 h after intravenous injection of [3H]4-PPBP parallels the in vitro binding of the radioligand in rat brain (pons/medulla > cerebellum > or = prefrontal cortex > or = parietal cortex > hypothalamus > olfactory tubercle > or = thalamus > hippocampus > striatum) [25].

References