Disease relevance of POU2F3

• Here we report the selective expression of two POU transcription factor genes, PLA-1 and OCT-1, in human placenta and choriocarcinoma cell lines JAR, JEG-3 and BeWo [1].
• The gene encoding the glycoprotein IIIa shows a common polymorphism PLA1/PLA2 that was variably associated with vascular disease [2].
• We were unable to detect OCT11 in human breast cancer cell lines using the anti rat Skn-1a/i antibody, although the expression of this gene in both human breast cancer cell lines and human primary breast tumors was detected by RT-PCR [3].
• OBJECTIVE: Fetal and neonatal alloimmune thrombocytopenia (AIT) caused by feto-maternal incompatibility at the HPA-1a (PLA-1) locus is well characterized [4].
• No soluble PLA1 antigen was found in the plasma of five patients with acute posttransfusion purpura [5].

High impact information on POU2F3

• In PA extracted from cells pretreated with 200 microM propranolol before stimulation with 1 microM FMLP, phospholipase A1 (PLA1)-digestion for 90 min, followed by quantitation of residual PA, showed that a minimum of 44% of PA in control (undigested) sample was diacyl-PA; alkylacyl-PA remained undigested by PLA1 [6].
• The expression pattern and mutant phenotype suggest that the PLA1 gene acting in developing leaf primordia affects the timing of successive leaf initiation and the termination of vegetative growth [7].
• The PLA1 epitope on platelet GPIIIa has a sulfhydryl-dependent conformation and is dependent on a leucine 33/proline33 polymorphism [8].
• GPIIIa-related PLA1 antigens with different molecular weights: studies in platelets, endothelial cells, and megakaryocytes [9].
• We conclude that the PLA1 antigen is present on a 120,000- as well as 100,000-mol wt glycoprotein of platelets and megakaryocytes, a 105,000-mol wt band of megakaryocytes, and a 100,000-mol wt glycoprotein of endothelial cells [9].

Biological context of POU2F3

• Pla-1 protein binds to a POU-consensus DNA sequence in the human placental lactogen-3 (PL-3) promoter and it is capable of trans-activating its transcription up to 18-fold [1].
• Aberrant promoter methylation and silencing of the POU2F3 gene in cervical cancer [10].
• Thus, aberrant DNA methylation of the CpG island in POU2F3 promoter appears to play a key role in silencing this gene expression in human CC [10].
• The results suggested that POU2F3 might be one of the CC-related tumor suppressor genes, which are disrupted by both epigenetic and genetic mechanisms [10].
• We now report that the loss of POU2F3 expression is tied to the hypermethylation of CpG islands in the POU2F3 promoter [10].

Anatomical context of POU2F3

• Immunohistochemical analysis on a cervical tissue microarray detected POU2F3 protein in the epithelium above the basal layer [10].
• The Skn-1a POU transcription factor is primarily expressed in keratinocytes of murine embryonic and adult epidermis [11].
• The Oct-11 gene is expressed during mouse embryogenesis and in the adult thymus and testis [12].
• In HeLa cells transfected with circular HPV16 DNA along with the expression plasmid for hSkn-1a, the transcript from P(670) was detectable, which indicates that the results obtained with the reporter plasmids are likely to have mimicked the regulation of P(670) in authentic HPV16 DNA [13].
• A similar differentiation-dependent distribution of expression has been reported for the recently cloned epithelial cell specific transcription factor Epoc-1/skn-1a [14].

Associations of POU2F3 with chemical compounds

• Bisulfite sequencing analysis revealed that methylation of specific CpG sites (-287 to -70 bp) correlated with POU2F3 expression, which could be reactivated with a demethylating agent [10].
• While maintained for several days in the presence of doxycycline, the HeLa/hSkn-1a cells showed a slightly prolonged time of population doubling, the occasional appearance of flat cells with lowered DNA synthesis, and a low level of apoptotic DNA fragmentation [15].
• A colony inhibition assay showed that the growth of HeLa S3, SiHa, CaSki, and C-33A cells was repressed, as seen from the decreased number and average size of the drug-resistant colonies at 2 or 3 weeks after transfection with a plasmid that can express hSkn-1a and neomycin resistance gene [15].
• Both mPA-PLA1beta and mPA-PLA1alpha recombinant proteins exhibited PA-specific PLA1 activity and were vanadate-sensitive [16].
• Additionally, these data suggest that the combined actions of PLA1 and the 95-kDa protein generate significant amounts of free arachidonic acid in the brain [17].

Physical interactions of POU2F3

• Skn-1a and Skn-1d1 bound the SPRR2A octamer site with comparable affinity and functioned as transcriptional activators [18].
• YY1 complexing with a short DNA fragment having site 1 was displaced by hSkn-1a, indicating that hSkn-1a's affinity with site 1 was stronger than YY1's. Disrupting the binding sites by nucleotide substitutions raised the basal expression level of luciferase and decreased the enhancing effect of hSkn-1a [13].

Other interactions of POU2F3

• Decreased expression of POU2F3 and TRIM29 was found in some cervical tumors and CC cell lines [19].
• The POU domain proteins Oct1, Skn1a/i, and Oct6, which are abundantly expressed in the epidermal cells, act to both stimulate and repress transcription in a general and a cell type-specific mode [20].
• Displacement of YY1 by differentiation-specific transcription factor hSkn-1a activates the P(670) promoter of human papillomavirus type 16 [13].

Analytical, diagnostic and therapeutic context of POU2F3

• Monoclonal antibody LK-4 differentiates PLA1/PLA1 from PLA2/PLA2 platelet lysates on solid phase enzyme-linked immunosorbent assay (ELISA), as well as immunoblot [8].
• Footprint analyses and gel retardation assays demonstrated direct binding of Epoc-1/skn-1a to a hitherto uncharacterized site within this region [14].
• To clarify the role of PLA1/PLA2 polymorphism in coronary risk, a meta-analysis of published data was conducted [2].
• Nevertheless, very low PLA1 activities (< or = 5 U/L, most likely due to heparin perfusion therapy) could also be detected by palmitic and stearic acid release from the sn-1 position, leading to small changes in fatty acid release patterns of sera with low PLA activities [21].
• We find that the PLA1 antigen of stored blood is due to the presence of platelet fragments which can be removed by centrifugation and that divalent cation-chelating agents play no role in the apparent binding of these fragments to platelets [5].

References