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. 1987 May;7(5):1716–1724. doi: 10.1128/mcb.7.5.1716

Molecular genetics of androgen-dependent and -independent expression of mouse sex-limited protein.

J Stavenhagen, F Loreni, C Hemenway, M Kalff, D M Robins
PMCID: PMC365272  PMID: 3037333

Abstract

Genes of the mouse S locus encoding C4 (the fourth component complement) and Slp (sex-limited protein) show extensive homology but are distinct in their function and regulation. In some mouse strains, such as B10.D2, Slp is androgen regulated, whereas in others, such as B10.W7R, expression of Slp is constitutive. We have previously shown that the B10.W7R strain has multiple Slp genes. In this report, we present the structure of the single C4 and four Slp genes of the B10.W7R S locus and compare the upstream flanking regions by partial sequence analysis and function in transfection assays. Of the four Slp genes, three (Slpw7.A, Slpw7.B, and Slpw7.C) have upstream and promoter regions very similar to those of C4. The fourth Slp gene (Slpw7.D) is instead virtually identical to the androgen-regulated allele (Slpd from the B10.D2 mouse) in upstream regions. In particular, far-upstream sequences from both Slpd and Slpw7.D render the bacterial chloramphenicol acetyltransferase gene hormonally responsive upon transfection into mammary carcinoma cell lines. The upstream sequences between 2 to 3 kilobases of the Slp promoter initiate transcription from multiple sites when fused proximal to the chloramphenicol acetyltransferase gene, and these transcripts are threefold more abundant in the presence of androgen. This behavior is similar for Slpd and Slpw7.D, which suggests that Slpw7.D may be androgen regulated but that this is masked in vivo by constitutive expression of the other Slp genes. Nonhomologous recombination is implicated not only in expanding the copy number of C4 and Slp genes in the B10.W7R mouse but also in creating hybrid genes with regulatory features of C4 and structural features of Slp.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bullock P., Miller J., Botchan M. Effects of poly[d(pGpT).d(pApC)] and poly[d(pCpG).d(pCpG)] repeats on homologous recombination in somatic cells. Mol Cell Biol. 1986 Nov;6(11):3948–3953. doi: 10.1128/mcb.6.11.3948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carroll M. C., Belt K. T., Palsdottir A., Yu Y. Molecular genetics of the fourth component of human complement and steroid 21-hydroxylase. Immunol Rev. 1985 Oct;87:39–60. doi: 10.1111/j.1600-065x.1985.tb01144.x. [DOI] [PubMed] [Google Scholar]
  3. Cato A. C., Miksicek R., Schütz G., Arnemann J., Beato M. The hormone regulatory element of mouse mammary tumour virus mediates progesterone induction. EMBO J. 1986 Sep;5(9):2237–2240. doi: 10.1002/j.1460-2075.1986.tb04490.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dover G. Molecular drive: a cohesive mode of species evolution. Nature. 1982 Sep 9;299(5879):111–117. doi: 10.1038/299111a0. [DOI] [PubMed] [Google Scholar]
  5. Efrat S., Hanahan D. Bidirectional activity of the rat insulin II 5'-flanking region in transgenic mice. Mol Cell Biol. 1987 Jan;7(1):192–198. doi: 10.1128/mcb.7.1.192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamada H., Seidman M., Howard B. H., Gorman C. M. Enhanced gene expression by the poly(dT-dG).poly(dC-dA) sequence. Mol Cell Biol. 1984 Dec;4(12):2622–2630. doi: 10.1128/mcb.4.12.2622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hansen T. H., Shreffler D. C. Characterization of a constitutive variant of the murine serum protein allotype, Slp. J Immunol. 1976 Nov;117(5 Pt 1):1507–1513. [PubMed] [Google Scholar]
  9. Hemenway C., Kalff M., Stavenhagen J., Walthall D., Robins D. Sequence comparison of alleles of the fourth component of complement (C4) and sex-limited protein (Slp). Nucleic Acids Res. 1986 Mar 25;14(6):2539–2554. doi: 10.1093/nar/14.6.2539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hood L., Campbell J. H., Elgin S. C. The organization, expression, and evolution of antibody genes and other multigene families. Annu Rev Genet. 1975;9:305–353. doi: 10.1146/annurev.ge.09.120175.001513. [DOI] [PubMed] [Google Scholar]
  11. Lennon G. G., Perry R. P. C mu-containing transcripts initiate heterogeneously within the IgH enhancer region and contain a novel 5'-nontranslatable exon. Nature. 1985 Dec 5;318(6045):475–478. doi: 10.1038/318475a0. [DOI] [PubMed] [Google Scholar]
  12. Levi-Strauss M., Tosi M., Steinmetz M., Klein J., Meo T. Multiple duplications of complement C4 gene correlate with H-2-controlled testosterone-independent expression of its sex-limited isoform, C4-Slp. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1746–1750. doi: 10.1073/pnas.82.6.1746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lévi-Strauss M., Georgatsou E., Tosi M., Meo T. Gene-specific probes demonstrate selective duplications of the C4-Slp gene in the H-2S alleles associated with a testosterone-independent expression of this isotype. Immunogenetics. 1985;21(4):397–401. doi: 10.1007/BF00430804. [DOI] [PubMed] [Google Scholar]
  14. Maniatis T., Fritsch E. F., Lauer J., Lawn R. M. The molecular genetics of human hemoglobins. Annu Rev Genet. 1980;14:145–178. doi: 10.1146/annurev.ge.14.120180.001045. [DOI] [PubMed] [Google Scholar]
  15. Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
  16. Nakayama K., Nonaka M., Yokoyama S., Yeul Y. D., Pattanakitsakul S. N., Takahashi M. Recombination of two homologous MHC class III genes of the mouse (C4 and Slp) that accounts for the loss of testosterone dependence of sex-limited protein expression. J Immunol. 1987 Jan 15;138(2):620–627. [PubMed] [Google Scholar]
  17. Nathans J., Piantanida T. P., Eddy R. L., Shows T. B., Hogness D. S. Molecular genetics of inherited variation in human color vision. Science. 1986 Apr 11;232(4747):203–210. doi: 10.1126/science.3485310. [DOI] [PubMed] [Google Scholar]
  18. Nathans J., Thomas D., Hogness D. S. Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science. 1986 Apr 11;232(4747):193–202. doi: 10.1126/science.2937147. [DOI] [PubMed] [Google Scholar]
  19. Nonaka M., Kimura H., Yeul Y. D., Yokoyama S., Nakayama K., Takahashi M. Identification of the 5'-flanking regulatory region responsible for the difference in transcriptional control between mouse complement C4 and Slp genes. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7883–7887. doi: 10.1073/pnas.83.20.7883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nonaka M., Takahashi M., Natsuume-Sakai S., Nonaka M., Tanaka S., Shimizu A., Honjo T. Isolation of cDNA clones specifying the fourth component of mouse complement and its isotype, sex-limited protein. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6822–6826. doi: 10.1073/pnas.81.21.6822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ogata R. T., Sepich D. S. Murine sex-limited protein: complete cDNA sequence and comparison with murine fourth complement component. J Immunol. 1985 Dec;135(6):4239–4244. [PubMed] [Google Scholar]
  22. Robins D. M., Malissen M., Hood L., Ferreira A., Walthall D., Mitchell M. Multiple C4/Slp genes distinguished by expression after transfection. Mol Cell Biol. 1986 Jan;6(1):134–141. doi: 10.1128/mcb.6.1.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Robins D. M., Paek I., Seeburg P. H., Axel R. Regulated expression of human growth hormone genes in mouse cells. Cell. 1982 Jun;29(2):623–631. doi: 10.1016/0092-8674(82)90178-7. [DOI] [PubMed] [Google Scholar]
  24. Rosa P. A., Sepich D. S., Shreffler D. C., Ogata R. T. Mice constitutive for sex-limited protein (SLP) expression contain multiple Slp gene sequences. J Immunol. 1985 Jul;135(1):627–631. [PubMed] [Google Scholar]
  25. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sepich D. S., Noonan D. J., Ogata R. T. Complete cDNA sequence of the fourth component of murine complement. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5895–5899. doi: 10.1073/pnas.82.17.5895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shreffler D. C. The S region of the mouse major histocompatibility complex (H-2): genetic variation and functional role in complement system. Transplant Rev. 1976;32:140–167. doi: 10.1111/j.1600-065x.1976.tb00232.x. [DOI] [PubMed] [Google Scholar]
  28. Smith G. P. Unequal crossover and the evolution of multigene families. Cold Spring Harb Symp Quant Biol. 1974;38:507–513. doi: 10.1101/sqb.1974.038.01.055. [DOI] [PubMed] [Google Scholar]
  29. Stanley E. R., Palmer R. E., Sohn U. Development of methods for the quantitative in vitro analysis of androgen-dependent and autonomous Shionogi carcinoma 115 cells. Cell. 1977 Jan;10(1):35–44. doi: 10.1016/0092-8674(77)90137-4. [DOI] [PubMed] [Google Scholar]
  30. Tautz D., Renz M. Simple sequences are ubiquitous repetitive components of eukaryotic genomes. Nucleic Acids Res. 1984 May 25;12(10):4127–4138. doi: 10.1093/nar/12.10.4127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tosi M., Lévi-Strauss M., Georgatsou E., Amor M., Meo T. Duplications of complement and non-complement genes of the H-2S region: evolutionary aspects of the C4 isotypes and molecular analysis of their expression variants. Immunol Rev. 1985 Oct;87:151–183. doi: 10.1111/j.1600-065x.1985.tb01149.x. [DOI] [PubMed] [Google Scholar]
  32. Treco D., Arnheim N. The evolutionarily conserved repetitive sequence d(TG.AC)n promotes reciprocal exchange and generates unusual recombinant tetrads during yeast meiosis. Mol Cell Biol. 1986 Nov;6(11):3934–3947. doi: 10.1128/mcb.6.11.3934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wigler M., Sweet R., Sim G. K., Wold B., Pellicer A., Lacy E., Maniatis T., Silverstein S., Axel R. Transformation of mammalian cells with genes from procaryotes and eucaryotes. Cell. 1979 Apr;16(4):777–785. doi: 10.1016/0092-8674(79)90093-x. [DOI] [PubMed] [Google Scholar]
  34. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  35. Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]

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