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Expression of the Oct-2 transcription factor in mouse mammary gland and cloning and characterization of a novel Oct-2 isoform

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Abstract

Oct-2 is a member of the POU family of transcription factors, which specifically bind to the octamer DNA motif ATGCAAAT and its closely related sequences. Unlike its ubiquitous counterpart Oct-1, Oct-2 is thought to be expressed only in B lymphocytes and neuronal cells and is mainly involved in immunoglobulin gene expression. We show here that Oct-2 is also expressed in the epithelial cells of mouse mammary gland, and that this expression is developmentally regulated. Rapid amplification of cDNA ends and subsequent cDNA cloning indicate that the mammary gland expresses multiple Oct-2 isoforms, including a novel isoform, named Oct-2.7. Compared with Oct-2 (isoform 2.1), the deduced Oct-2.7 sequence has an additional 22 amino acids close to the N-terminus and a novel 76-amino-acid C-terminus resulting from alternative splicing, with retention of the last intron that is spliced out in all other isoforms. Although Oct-2.7 has intact POU-specific and POU-homeo domains, it is unable to bind to the octamer motif, unlike all other known isoforms. Like Oct-1, both Oct-2.1 and Oct-2.7 can activate basal β-casein gene promoter activity. However, activation by Oct-2.7, which is independent of DNA binding, is significantly lower than that by Oct-2.1. Moreover, deletion of the first 114 amino acids at the N-terminus of Oct-2.1 has no effect on activation; this does not support previous reports of the presence of an inhibitory domain in this region.

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References

  • Ahmad I, Hoessli DC, Walker-Nasir E, Rafik SM, Shakoori AR, Nasir-ud-Din (2006) Oct-2 DNA binding transcription factor: functional consequences of phosphorylation and glycosylation. Nucleic Acids Res 34:175–184

    Article  PubMed  CAS  Google Scholar 

  • Annweiler A, Zwilling S, Wirth T (1994) Functional differences between the Oct2 transactivation domains determine the transactivation potential of individual Oct2 isoforms. Nucleic Acids Res 22:4250–4258

    Article  PubMed  CAS  Google Scholar 

  • Chapman CM, Latchman DS (1998) The different alternatively spliced isoforms of the Oct-2 transcription factor repress the involucrin promoter in a cell type-specific manner. Mol Biol Rep 25:253–257

    Article  PubMed  CAS  Google Scholar 

  • Clerc RG, Corcoran LM, LeBowitz JH, Baltimore D, Sharp PA (1988) The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains. Genes Dev 2:1570–1581

    Article  PubMed  CAS  Google Scholar 

  • Corcoran LM, Karvelas M, Nossal GJ, Ye ZS, Jacks T, Baltimore D (1993) Oct-2, although not required for early B-cell development, is critical for later B-cell maturation and for postnatal survival. Genes Dev 7:570–582

    Article  PubMed  CAS  Google Scholar 

  • Corcoran LM, Koentgen F, Dietrich W, Veale M, Humbert PO (2004) All known in vivo functions of the Oct-2 transcription factor require the C-terminal protein domain. J Immunol 172:2962–2969

    PubMed  CAS  Google Scholar 

  • Dong B, Zhao F-Q (2007) Involvement of the ubiquitous Oct-1 transcription factor in hormonal induction of beta-casein gene expression. Biochem J 401:57–64

    Article  PubMed  CAS  Google Scholar 

  • Friedl EM, Matthias P (1995) Transcriptional activation and repression, two properties of the lymphoid-specific transcription factor Oct-2a. Eur J Biochem 234:308–316

    Article  PubMed  CAS  Google Scholar 

  • Gay RD, Dawson SJ, Latchman DS (1997) The different inhibitory domains of the Oct-2 transcription factor have distinct functional activities. FEBS Lett 416:135–138

    Article  PubMed  CAS  Google Scholar 

  • Goldsborough AS, Healy LE, Copeland NG, Gilbert DJ, Jenkins NA, Willison KR, Ashworth A (1993) Cloning, chromosomal localization and expression pattern of the POU domain gene Oct-11. Nucleic Acids Res 21:127–134

    Article  PubMed  CAS  Google Scholar 

  • Hatzopoulos AK, Stoykova AS, Erselius JR, Goulding M, Neuman T, Gruss P (1990) Structure and expression of the mouse Oct2a and Oct2b, two differentially spliced products of the same gene. Development 109:349–362

    PubMed  CAS  Google Scholar 

  • Inamoto S, Segil N, Pan ZQ, Kimura M, Roeder RG (1997) The cyclin-dependent kinase-activating kinase (CAK) assembly factor, MAT1, targets and enhances CAK activity on the POU domains of octamer transcription factors. J Biol Chem 272:29852–29858

    Article  PubMed  CAS  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 277:680–685

    Article  Google Scholar 

  • Latchman DS (1996) The Oct-2 transcription factor. Int J Biochem Cell Biol 28:1081–1083

    Article  PubMed  CAS  Google Scholar 

  • Latchman DS (1999) POU family transcription factors in the nervous system. J Cell Physiol 179:126–133

    Article  PubMed  CAS  Google Scholar 

  • Lillycrop KA, Latchman DS (1992) Alternative splicing of the Oct-2 transcription factor RNA is differentially regulated in neuronal cells and B cells and results in protein isoforms with opposite effects on the activity of octamer/TAATGARAT-containing promoters. J Biol Chem 267:24960–24965

    PubMed  CAS  Google Scholar 

  • Lillycrop KA, Latchman DS (1995) The inhibitory domain in the Oct-2 transcription factor represses gene activity in a cell type-specific and promoter-independent manner. Mol Biol Rep 21:87–94

    Article  PubMed  CAS  Google Scholar 

  • Lillycrop KA, Dawson SJ, Estridge JK, Gerster T, Matthias P, Latchman DS (1994) Repression of a Herpes simplex virus immediate-early promoter by the Oct-2 transcription factor is dependent on an inhibitory region at the N terminus of the protein. Mol Cell Biol 14:7633–7642

    PubMed  CAS  Google Scholar 

  • Liu YZ, Lillycrop KA, Latchman DS (1995) Regulated splicing of the Oct-2 transcription factor RNA in neuronal cells. Neurosci Lett 183:8–12

    Article  PubMed  CAS  Google Scholar 

  • Meijer D, Graus A, Kraay R, Langeveld A, Mulder MP, Grosveld G (1990) The octamer binding factor Oct6: cDNA cloning and expression in early embryonic cells. Nucleic Acids Res 18:7357–7365

    Article  PubMed  CAS  Google Scholar 

  • Muller-Immergluck MM, Schaffner W, Matthias P (1991) Transcription factor Oct-2A contains functionally redundant activating domains and works selectively from a promoter but not from a remote enhancer position in non-lymphoid (HeLa) cells. EMBO J 9:1625–1634

    Google Scholar 

  • Prefontaine GG, Walther R, Giffin W, Lemieux ME, Pope L, Hache RJ (1999) Selective binding of steroid hormone receptors to octamer transcription factors determines transcriptional synergism at the mouse mammary tumor virus promoter. J Biol Chem 274:26713–26719

    Article  PubMed  CAS  Google Scholar 

  • Rijnkels M, Wheeler DA, de Boer HA, Pieper FR (1997) Structure and expression of the mouse casein gene locus. Mamm Genome 8:9–15

    Article  PubMed  CAS  Google Scholar 

  • Rosner MH, Vigano MA, Ozato K, Timmons PM, Poirier F, Rigby PW, Staudt LM (1990) A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature 345:686–692

    Article  PubMed  CAS  Google Scholar 

  • Scholer HR (1991) Octamania: the POU factors in murine development. Trends Genet 7:323–329

    PubMed  CAS  Google Scholar 

  • Scholer HR, Hatzopoulos AK, Balling R, Suzuki N, Gruss P (1989) A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J 8:2543–2550

    PubMed  CAS  Google Scholar 

  • Schonemann MD, Ryan AK, Erkman L, McEvilly RJ, Bermingham J, Rosenfeld MG (1998) POU domain factors in neural development. Adv Exp Med Biol 449:39–53

    PubMed  CAS  Google Scholar 

  • Schreiber E, Matthias P, Muller MM, Schaffner W (1989) Rapid detection of octamer binding proteins with “mini-extracts”, prepared from a small number of cells. Nucleic Acids Res 17:6419

    Article  PubMed  CAS  Google Scholar 

  • Schubart K, Massa S, Schubart D, Corcoran LM, Rolink AG, Matthias P (2001) B cell development and immunoglobulin gene transcription in the absence of Oct-2 and OBF-1. Nat Immunol 2:69–74

    Article  PubMed  CAS  Google Scholar 

  • Sharif MN, Radomska HS, Miller DM, Eckhardt LA (2001) Unique function for carboxyl-terminal domain of Oct-2 in Ig-secreting cells. J Immunol 167:4421–4429

    PubMed  CAS  Google Scholar 

  • Sturm RA, Das G, Herr W (1988) The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev 2:1582–1599

    Article  PubMed  CAS  Google Scholar 

  • Veenstra GJ, van der Vliet PC, Destree OH (1997) POU domain transcription factors in embryonic development. Mol Biol Rep 24:139–155

    Article  PubMed  CAS  Google Scholar 

  • Verrijzer CP, van der Vliet PC (1993) POU domain transcription factors. Biochim Biophys Acta 1173:1–21

    PubMed  CAS  Google Scholar 

  • Verrijzer CP, Alkema MJ, van Weperen WW, van Leeuwen HC, Strating MJ, van der Vliet PC (1992a) The DNA binding specificity of the bipartite POU domain and its subdomains. EMBO J 11:4993–5003

    PubMed  CAS  Google Scholar 

  • Verrijzer CP, Oosterhout JA van, Vliet PC van der (1992b) The Oct-1 POU domain mediates interactions between Oct-1 and other POU proteins. Mol Cell Biol 12:542–551

    PubMed  CAS  Google Scholar 

  • Wirth T, Priess A, Annweiler A, Zwilling S, Oeler B (1991) Multiple Oct2 isoforms are generated by alternative splicing. Nucleic Acids Res 19:43–51

    Article  PubMed  CAS  Google Scholar 

  • Zhao F-Q, Adachi K, Oka T (2002) Involvement of Oct-1 in transcriptional regulation of beta-casein gene expression in mouse mammary gland. Biochim Biophys Acta 1577:27–37

    PubMed  CAS  Google Scholar 

  • Zhao F-Q, Zheng Y, Dong B, Oka T (2004) Cloning, genomic organization, expression, and effect on beta-casein promoter activity of a novel isoform of the mouse Oct-1 transcription factor. Gene 326:175–187

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank the staff at the Vermont Cancer Center DNA Analysis Facility for DNA sequencing services.

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Correspondence to Feng-Qi Zhao.

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This work was supported by Vermont Cancer Center and the University of Vermont Agricultural Experimental Station.

The nucleotide sequence of the novel Oct-2 isoform 2.7 reported in this paper has been submitted to GenBank with assigned accession number AY746974.

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Dong, B., Zhao, FQ. Expression of the Oct-2 transcription factor in mouse mammary gland and cloning and characterization of a novel Oct-2 isoform. Cell Tissue Res 328, 595–606 (2007). https://doi.org/10.1007/s00441-006-0368-0

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