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POU DOMAIN, CLASS 2, TRANSCRIPTION FACTOR 2; POU2F2

POU DOMAIN, CLASS 2, TRANSCRIPTION FACTOR 2; POU2F2

Alternative titles; symbolsOTF, LYMPHOID-SPECIFIC, 2; OTF2OCTAMER-BINDING TRANSCRIPTION FACTOR 2; OCT2HGNC Approved Gene Symbol: POU2F2Cytogenetic location: 19q1...

Alternative titles; symbols

  • OTF, LYMPHOID-SPECIFIC, 2; OTF2
  • OCTAMER-BINDING TRANSCRIPTION FACTOR 2; OCT2

HGNC Approved Gene Symbol: POU2F2

Cytogenetic location: 19q13.2 Genomic coordinates (GRCh38): 19:42,086,109-42,197,930 (from NCBI)

▼ Cloning and Expression

An understanding of development necessitates an understanding of the molecular mechanisms of cell type-specific gene expression. Using synthetic promoter constructions, it has been found that 2 sequences within immunoglobulin promoters are sufficient for lymphoid-specific promoter activity: an octamer, ATTTGCAT, and a TATA box. Staudt et al. (1988) isolated a cDNA which hybridized with mRNA transcripts that were largely restricted to lymphoid cells. The level of expression of the gene, termed OCT2, within different lymphoid cell lines correlated well with the amount of a nuclear factor called NFA2 that had previously been detected only in lymphoid cells.

Ko et al. (1988) determined the DNA sequence of the OCT2 cDNA and showed that its gene product contains a homeobox. Site-directed mutagenesis of the homeobox domain abolished DNA binding.

▼ Gene Function

Deans et al. (1996) identified the neuronal NOS gene (163731) as a target of OCT2 transcriptional activation in neuronal cells.

By screening a human T-cell cDNA expression library, Terunuma et al. (1997) identified the zinc finger protein T86 (ZNF593; 616698) as a factor that reversed OCT2-dependent transcriptional repression. Using a gel mobility shift assay, they found that coexpression of T86 with OCT2 interfered with DNA binding by OCT2. Deletion analysis revealed that the central POU domain of OCT2 was required for T86-mediated reversal of OCT2-dependent gene repression. T86 did not appear to bind DNA itself. Cotranslation of T86 and OCT2 appeared to be required for T86-mediated inhibition of OCT2 repression.

Mok et al. (2013) detected markedly upregulated expression of microRNA-210 (MIR210; 612982) in activated mouse B cells, in contrast with other miRNAs that were downregulated in such cells. Chromatin immunoprecipitation analysis demonstrated binding of Oct2 to the Mir210 promoter in mouse B-lymphoma cells and enriched histone modification, suggesting promoter activity. Activation of Oct2-deficient B cells resulted in reduced Mir210 expression compared with wildtype B cells. Mice lacking Mir210 developed autoantibodies by 5 months of age. Overexpression of Mir210 caused an increase in B1 cells, which spontaneously produce Ig, no change in the number of B2 cells, which have low spontaneous Ig production, and a reduction in marginal zone B cells. B2-cell fitness was reduced by Mir210 overexpression. Mir210 overexpression also resulted in impaired production of class-switched antibodies. In vitro studies demonstrated defects in cellular proliferation and cell cycle entry, consistent with transcriptomic analysis that indicated downregulation of the genes involved in cellular proliferation. Mok et al. (2013) concluded that OCT2, which induces MIR210, inhibits autoantibody production.

▼ Mapping

Ko et al. (1988) demonstrated that the OCT2 gene is located on chromosome 19, using hybridization to a panel of somatic cell hybrid DNAs.

By linkage studies in an interspecific backcross and by studies of recombinant inbred strains, Siracusa et al. (1991) assigned the Otf2 gene to mouse chromosome 7. Whereas the Otf1 and Otf2 molecular probes recognize single loci, members of the Otf3 family map to mouse chromosomes 1, 2, 3, 6, 14, 17, and the X chromosome.

▼ Animal Model

Schubart et al. (2001) noted that Oct2-deficient mice die at birth but have normal B-cell development and transcription of immunoglobulin (Ig) genes. Oct-binding factor-1 (Obf1; 601206)-deficient mice are viable with unaffected B-cell development in bone marrow and normal serum IgM but have reduced B-cell numbers in spleen and low serum IgG. By creating double knockout mice, Schubart et al. (2001) confirmed that B-cell development and Ig gene transcription can proceed normally without these B-cell specific factors. However, in these animals the mature B-cell pool was strongly reduced, suggesting that these factors play an important role in controlling the expansion and/or maintenance of mature B cells.

Tags: 19q13.2