Disease relevance of Pou3f4

• To clarify the role of neuropeptides in dyskinesia induced by iminodipropionitrile (IDPN), the levels of five representative neuropeptides were examined in discrete regions of the rat brain 4 weeks after intraperitoneal injection of IDPN [1].
• To test the hypothesis that this increased activity is due to hypoxic hypoxia per se, we subjected pregnant dams to inspired carbon monoxide concentrations ranging from 150 to 1000 ppm and assayed ODC activity in the fetal brain 4 h later [2].

High impact information on Pou3f4

• Brn-4 was shown to bind to DNA sequences containing the octamer motif and to trans-activate promoters containing this DNA binding motif, based on the actions of a unique N-terminal information [3].
• A cDNA encoding a new member of the POU-III class of the POU domain gene family, referred to as Brn-4, was isolated from a rat hypothalamic cDNA library [3].
• Regulation of striatal D1A dopamine receptor gene transcription by Brn-4 [4].
• Both these sites are essential for transactivation by Brn-4 because deletion of either significantly reduced this enhancer activity [4].
• Gel mobility-shift assays using glutathione S-transferase-Brn-4 fusion protein indicated that Brn-4 binds to these sequences [4].

Biological context of Pou3f4

• Gel mobility-supershift assay using rat striatal nuclear extract and Brn-4 antibody confirmed the presence of Brn-4 in this brain region and its ability to bind to its consensus sequences in the D1A gene [4].
• Transcriptional transactivation experiments reveal that brain 4 is a major regulator of proglucagon gene expression by its interaction with the G1 element [5].
• The absence of Pdx1 and the expression of brain-4 distinguish alpha-cells from other pancreatic endocrine cell lineages [6].
• To define the transcription factor responsible for pancreatic cell differentiation, we employed the reverse tetracycline-dependent transactivator system in INS-I cell-derived subclones INSralphabeta and INSrbeta to achieve tightly controlled and conditional expression of wild type Pdx1 or its dominant-negative mutant, as well as brain-4 [6].

Anatomical context of Pou3f4

• Brn-4 is a member of the POU transcription factor family and is expressed in the central nervous system [4].
• In an attempt to identify major homeodomain proteins involved in pancreatic alpha-cell-specific proglucagon expression, we found that the POU domain transcription factor brain 4 is abundantly expressed in proglucagon-producing islet cell lines and rat pancreatic islets [5].

Associations of Pou3f4 with chemical compounds

• When infused intraventricularly for 2 hr, DF and DNF at 500 but not at 125 250 micrograms/hr, markedly reduced concentrations of 5-HT in brain 4 hr after the end of the infusion [7].
• Brain dopamine turnover was also inhibited at higher doses as judged by the alpha-methyl-p-tyrosine method and by a decrease in the concentration of HVA in the rat brain 4 h after medetomidine [8].
• Male 3-month-old Wistar rats dosed i.p. with 200 mg/kg of nitromethane or -ethane showed increased acid proteinase activity in the brain 4 h after the injection [9].

Other interactions of Pou3f4

• Electrophoretic mobility shift assays with specific antisera identify brain 4 as a major constituent of nuclear proteins of glucagon-producing cells that bind to the G1 element of the proglucagon gene proximal promoter [5].

Analytical, diagnostic and therapeutic context of Pou3f4

• In situ hybridization revealed colocalization of Brn-4 and D1A mRNAs at the level of a single neuron in the rat striatum where this dopamine receptor is most abundantly expressed [4].

References