Disease relevance of Pou2f1

• We report the cDNA cloning of the human oct-1 gene, which encodes Oct-1, by screening lambda gt11 recombinant phage in situ for octamer motif-specific DNA binding [1].
• Herpes simplex virus infections are arrested in Oct-1-deficient cells [2].
• Oct-1 protein promotes functional transcription complex assembly on the mouse mammary tumor virus promoter [3].
• The plasma concentration of metformin exhibited similar time profiles between the wild-type and Oct1(-/-) mice, suggesting that the liver is the key organ responsible for the lactic acidosis [4].

High impact information on Pou2f1

• We suggest that Oct-3 is a novel octamer binding transcription factor that is developmentally regulated during mouse embryogenesis [5].
• One previously characterized form (NF-A1) was found in all cell lines tested while the other form (NF-A2) was restricted to lymphoid cell lines [6].
• Deletion analysis of the 743-amino-acid-long oct-1 open reading frame shows that the DNA-binding activity lies within a central highly charged domain of 160 amino acids [1].
• Targeted disruption of the CD3 eta locus causes high lethality in mice: modulation of Oct-1 transcription on the opposite strand [7].
• Although differences in tissue distribution and DNA binding capacity of Oct-1 between wild-type and eta-deficient mice were not evident from in situ hybridization and gel shift analysis, the high mortality in the eta-deficient strain may well be due to the disturbance of Oct-1 transcription by the mutation in the zeta/eta locus [7].

Biological context of Pou2f1

• The POU homeodomain transcription factor Oct-1 is essential for activity of the gonadotropin-releasing hormone neuron-specific enhancer [8].
• Oct1 and Emb, a class VI POU domain protein, bind to consensus sites on the DNA, and it is the binding of Emb which is important for activity [9].
• Although we demonstrate expression of a number of POU homeodomain genes in GT1 cells, a supershift assay with Oct-1 antibody demonstrates that Oct-1 is the protein binding the enhancer [8].
• The glucocorticoid receptor is tethered to DNA-bound Oct-1 at the mouse gonadotropin-releasing hormone distal negative glucocorticoid response element [10].
• Molecular probes for Otf-1 and Otf-2 recognized single loci on mouse chromosomes 1 and 7, respectively, whereas probes for Otf-3 recognized a minimum of eight independently segregating loci (designated Otf-3a through Otf-3h) [11].

Anatomical context of Pou2f1

• Oct-3 has a conserved POU domain, but the remaining part is distinct from other POU domain-containing proteins such as Oct-1 and Oct-2. mRNA of 1.5 kb coding for Oct-3 is abundant in P19 stem cells but is dramatically repressed during RA-induced differentiation [5].
• This octamer element can be bound by either Oct-1 or Oct-2 but requires the expression of Oct-2 to activate transcription in B cells [12].
• Here, HSV infection of Oct-1-deficient mouse embryonic fibroblast cells demonstrates that Oct-1 is critical for IE gene expression at low multiplicities of infection (moi) [2].
• Oct-1-deficient embryos died during gestation, frequently appeared anemic, and suffered from a lack of Ter-119-positive erythroid precursor cells [13].
• The mechanism of transcriptional activation by Oct-1 was investigated using in vitro transcription assays with a HeLa cell nuclear extract depleted of endogenous Oct-1 [3].

Associations of Pou2f1 with chemical compounds

• Oct3 is an embryonic octamer-binding transcription factor, whose expression is rapidly repressed by retinoic acid (RA) [14].
• Consistent with this finding, Oct-1-deficient fibroblasts were hypersensitive to gamma radiation, doxorubicin, and hydrogen peroxide and harbored elevated reactive oxygen species [15].
• Finally, experiments designed to exploit the sensitivity of discrete steps in transcription complex assembly to the anionic detergent Sarkosyl demonstrated that Oct-1 must be present during formation of an early intermediate in the assembly process [3].
• When mice were given metformin, the blood lactate concentration significantly increased in the wild-type mice, whereas only a slight increase was observed in Oct1(-/-) mice [4].
• Whereas one clone (oct-1a) was very similar to its human oct-1 homologue, the other (oct-1b), contained an additional 72 bp sequence (designated E1) at the serine threonine rich coding region (position 1485 of the human oct-1), and a deletion of another 72 bp sequence (designated E2) downstream (position 1920) [16].

Physical interactions of Pou2f1

• Thus, Oct-1 binds to the GnRH enhancer in vitro, and this binding is critical to the transcriptional activity of this neuron-specific enhancer in GT1 cells [8].
• As a result, the Oct2b protein has a carboxy end which is similar to that of the ubiquitous octamer-binding protein Oct1 [17].
• Progesterone receptor bound to the HRE facilitates binding of OTF-1 to the two octamer motifs [18].

Regulatory relationships of Pou2f1

• Our results demonstrate that in these Oct2-deficient B cells the ubiquitous endogenous Oct1 protein is able to stimulate octamer-containing promoters to a level comparable with that of normal Oct2-positive B cells [19].

Other interactions of Pou2f1

• The mRNAs of two additional POU genes, Emb (POU class VI) and Oct-1 (POU class II), were also expressed in developing muscle and, unlike Brn-4, continued to be expressed in postnatal and adult muscles [20].
• Oct-1, silencer sequence, and GC box regulate thyroid hormone receptor beta1 promoter [21].
• Mutation of the silencer response element, mutation of the GC box, and Oct-1 over expression in COS 1 cells increased TR beta1 promoter function as assayed by Luciferase reporter [21].
• The proteins, which were not recognized by an anti-Oct-1 antibody, may be involved in regulation of the initiation of DNA replication in the IgH gene [22].
• To study the role of Oct-1 in these processes, the lymphoid compartment of RAG-1(-/-) animals was reconstituted with Oct-1-deficient fetal liver hematopoietic cells [23].

Analytical, diagnostic and therapeutic context of Pou2f1

• To address the role of Oct-1 in vivo, an Oct-1-deficient mouse strain was generated by gene targeting [13].
• As shown by gel retardation assay, Oct-1, Oct-2, and some unknown proteins from myeloma cell line NS/0 interact with the TAAT-core sites of these clusters [24].
• The nfa1 gene was cloned from a cDNA library of pathogenic Naegleria fowleri by immunoscreening; it consisted of 360 bp and produced a 13.1 kDa recombinant protein (rNfa1) that showed the pseudopodia-specific localization by immunocytochemistry in the previous study [25].

References