Disease relevance of POU2F1

• The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain [1].
• Thus, the DRA promoter discriminates against OTF-1 activation at the level of DNA binding in the glioblastoma line [2].
• The ubiquitous and constitutive octamer transcription factor OTF-1 (Oct 1) is the target of positive regulation by the potent herpes simplex virus trans-activator VP16, which forms a complex with the homeodomain of OTF-1 [3].
• Glucocorticoid receptor (GR) and octamer transcription factors 1 and 2 (Oct-1/2) interact synergistically to activate the transcription of mouse mammary tumor virus and many cellular genes [4].
• VP16 forms a complex with cellular factors (Oct1 and host cell factor [HCF]) and TAATGARAT elements (found in all HSV-1 IE promoter/enhancer sequences) to mediate stimulation of IE transcription [5].

High impact information on POU2F1

• Surprisingly, p38 represents a nuclear form of glyceraldehyde-3-phosphate dehydrogenase, and binding to Oct-1, as well as OCA-S function, is stimulated by NAD(+) but inhibited by NADH [6].
• We have isolated and functionally characterized a multicomponent Oct-1 coactivator, OCA-S which is essential for S phase-dependent histone H2B transcription [6].
• Histone gene expression in mammalian cells is codependent upon the Oct-1 transcription factor and its cognate, OCA-S coactivator complex [7].
• Here we show that the MMTV promoter contains two degenerated octamer motifs immediately upstream of the TATA box that together bind OTF-1 (Oct-1, NFIII) with an affinity similar to the octamer consensus [8].
• Purification and characterization of OTF-1, a transcription factor regulating cell cycle expression of a human histone H2b gene [9].

Chemical compound and disease context of POU2F1

• Nonfimbrial, mannose-resistant hemagglutinins (nonfimbrial adhesions [NFA] NFA-1 and NFA-2) were extracted from two agar-grown urinary isolates of Escherichia coli strains 827 (O83:K1:H4) and 54 (O14:K?:H11) [10].

Biological context of POU2F1

• All of these factors (GR, c-Jun, OCT-1) have transcription activation domains, but STAT3 is required for the observed transcriptional increase [11].
• Expression of Oct-1 stimulates reporter gene expression from the T and the C-13,910 variant/LPH promoter constructs only when it is co-expressed with HNF1alpha [12].
• The data suggest that the binding of Oct-1 to the T-13,910 variant directs increased lactase promoter activity and this might provide an explanation for the lactase persistence phenotype in the human population [12].
• Protein-DNA binding studies on DHS3 revealed that octamer transcription factor 1 (OCT-1) and GATA-4 bound site 7, in vitro, and transient transfection analysis showed that their binding sites were required for silencing activity [13].
• Antibody supershift and Southwestern blot assays confirmed that the protein binding to the octamer sequence was the ubiquitously expressed transcription factor Oct-1 [14].

Anatomical context of POU2F1

• We now explored the effect of two different statins, simvastatin and atorvastatin, in the activation of the octamer transcription factor Oct-1 on the monocytic cell line THP-1 [15].
• The human OTF1 locus encoding the Oct-1 protein has previously been mapped to chromosome 1 cen-->q32 by analysis of somatic cell hybrids [16].
• Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene [17].
• In an attempt to understand the apparent transcriptional selectivity of these factors, we have investigated the physical and functional characteristics of OTF-1 purified from HeLa cells and both OTF-1 and OTF-2 purified from B cells [18].
• Nuclear OCT-1 immunoreactivity was seen in normal B cells, in many extrafollicular T cells, and in a heterogeneous pattern (ranging in intensity from weak to moderate) in most T-cell neoplasms [19].

Associations of POU2F1 with chemical compounds

• Our results indicate that simvastatin and atorvastatin increase the activity of the transcriptional repressor Oct-1 in mononuclear cells, and could thus contribute to decrease the activation of these cells [15].
• Functional interaction between Oct-1 and retinoid X receptor [20].
• Furthermore, cotransfected unliganded thyroid hormone receptor enhanced the transactivation by Oct-1, and addition of 3,3',5-tri-iodo-l-thyronine obliterated the stimulatory effects [21].
• The activation required binding of OTF-1/OTF-2, and C4 could not stimulate transcription by itself, implying a synergistic interaction [22].
• On denaturing polyacrylamide gels OTF-1 and NFIII exhibit identical mobility [23].

Physical interactions of POU2F1

• T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro [12].
• Supershift analyses show that Oct-1 binds directly to the T-13,910 variant, and we suggest that GAPDH is co-purified due to interactions with Oct-1 [12].
• STAT5 and Oct-1 form a stable complex that modulates cyclin D1 expression [24].
• Site-directed mutagenesis of a putative octamer-binding transcription factor binding site located within this latter region led to a strong decrease of the transcriptional activity of the SBEM promoter [25].
• 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase the binding activity and nuclear level of Oct-1 in mononuclear cells [15].

Regulatory relationships of POU2F1

• Accordingly, Oct-1 also potently enhances transcriptional activation mediated by a Ser133Ala CREB mutant [26].
• In this report, we used Oct-1 antisense transformants to determine that Oct-1 represses the interferon-gamma response of the endogenous HLA-DRA gene [27].
• HCF binds directly to VP16 and this promotes subsequent interaction of the VP16-HCF complex with the POU DNA-binding domain of Oct-1 and selective assembly onto target sites [28].
• Here we present evidence that the glucocorticoid receptor can negatively regulate OTF-1 function by a mechanism that is independent of DNA binding [3].
• Oct2 can stimulate transcription in B-cell nuclear extracts and in HeLa nuclear extracts depleted of the ubiquitous factor Oct1 by wheat germ lectin affinity chromatography [29].

Other interactions of POU2F1

• Based on our biochemical data, we propose a mode of OBF1-Oct1 dimer interaction, suggesting a novel arrangement of the subdomain connectivities [30].
• GATA-1 and Oct-1 are required for expression of the human alpha-hemoglobin-stabilizing protein gene [31].
• Both OCT-1 and CAAT motifs are able to confer BRCA1 inducibility in a non-related minimal promoter [32].
• BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs [32].
• We had previously shown that the ubiquitous Oct1 and the lymphoid-specific Oct2 transcription factors stimulate transcription at the level of stable preinitiation complex formation [33].

Analytical, diagnostic and therapeutic context of POU2F1

• Furthermore, chromatin immunoprecipitation revealed that OCT-1 bound to site 7 in the endogenous gene, but only in myoid cells [13].
• Low concentrations of both statins increased Oct-1 DNA binding activity (electrophoretic mobility shift assay) that was resolved into two specific bands [15].
• Both statins increased Oct-1 and Oct-2 nuclear protein levels (Western blot) [15].
• We report here the regional localization of OTF1 to 1q22-->q23 by fluorescence in situ hybridization [16].
• On the basis of an idea that the pseudopodia-specific Nfa1 protein seems to be involved in the pathogenicity of N. fowleri, the cytopathic activity of N. fowleri trophozoites co-cultured with rat microglial cells was observed, and the effects of an anti-Nfa1 antibody in a co-culture system were elucidated [34].

References