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. 1987 Sep;6(9):2773–2779. doi: 10.1002/j.1460-2075.1987.tb02572.x

Coincident start sites for divergent transcripts at a randomly selected CpG-rich island of mouse.

P Lavia 1, D Macleod 1, A Bird 1
PMCID: PMC553702  PMID: 2445562

Abstract

We determined the nucleotide sequence of two HTF islands that were selected at random from mouse chromosomal DNA. Both were non-methylated, G + C rich, and contained CpG at close to the expected frequency. When used as probes, the two islands detected multiple transcripts in RNA from several mouse tissues. Cloned cDNAs for the major transcripts of one island (HTF9) were isolated and used to construct a transcriptional map. We found that HTF9 contains the origin of a pair of divergent transcripts that are probably messenger RNAs. The bidirectional promoter is different from those previously observed as the major transcription start sites for each orientation are coincident on opposite strands of the DNA. The results support the view that HTF islands often mark genes, and they suggest that bidirectional transcription may be a common feature of island promoters.

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Selected References

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  1. Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
  2. Bird A. P., Taggart M. H., Nicholls R. D., Higgs D. R. Non-methylated CpG-rich islands at the human alpha-globin locus: implications for evolution of the alpha-globin pseudogene. EMBO J. 1987 Apr;6(4):999–1004. doi: 10.1002/j.1460-2075.1987.tb04851.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bird A., Taggart M., Frommer M., Miller O. J., Macleod D. A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell. 1985 Jan;40(1):91–99. doi: 10.1016/0092-8674(85)90312-5. [DOI] [PubMed] [Google Scholar]
  4. Brown W. R., Bird A. P. Long-range restriction site mapping of mammalian genomic DNA. 1986 Jul 31-Aug 6Nature. 322(6078):477–481. doi: 10.1038/322477a0. [DOI] [PubMed] [Google Scholar]
  5. Cooper D. N., Taggart M. H., Bird A. P. Unmethylated domains in vertebrate DNA. Nucleic Acids Res. 1983 Feb 11;11(3):647–658. doi: 10.1093/nar/11.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crouse G. F., Leys E. J., McEwan R. N., Frayne E. G., Kellems R. E. Analysis of the mouse dhfr promoter region: existence of a divergently transcribed gene. Mol Cell Biol. 1985 Aug;5(8):1847–1858. doi: 10.1128/mcb.5.8.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Farnham P. J., Abrams J. M., Schimke R. T. Opposite-strand RNAs from the 5' flanking region of the mouse dihydrofolate reductase gene. Proc Natl Acad Sci U S A. 1985 Jun;82(12):3978–3982. doi: 10.1073/pnas.82.12.3978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  9. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  10. Giguére V., Isobe K., Grosveld F. Structure of the murine Thy-1 gene. EMBO J. 1985 Aug;4(8):2017–2024. doi: 10.1002/j.1460-2075.1985.tb03886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  12. Kolsto A. B., Kollias G., Giguere V., Isobe K. I., Prydz H., Grosveld F. The maintenance of methylation-free islands in transgenic mice. Nucleic Acids Res. 1986 Dec 22;14(24):9667–9678. [PMC free article] [PubMed] [Google Scholar]
  13. Kozak M. Bifunctional messenger RNAs in eukaryotes. Cell. 1986 Nov 21;47(4):481–483. doi: 10.1016/0092-8674(86)90609-4. [DOI] [PubMed] [Google Scholar]
  14. McKeon C., Ohkubo H., Pastan I., de Crombrugghe B. Unusual methylation pattern of the alpha 2 (l) collagen gene. Cell. 1982 May;29(1):203–210. doi: 10.1016/0092-8674(82)90104-0. [DOI] [PubMed] [Google Scholar]
  15. Meinkoth J., Wahl G. Hybridization of nucleic acids immobilized on solid supports. Anal Biochem. 1984 May 1;138(2):267–284. doi: 10.1016/0003-2697(84)90808-x. [DOI] [PubMed] [Google Scholar]
  16. Melton D. W., Konecki D. S., Brennand J., Caskey C. T. Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2147–2151. doi: 10.1073/pnas.81.7.2147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Melton D. W., McEwan C., McKie A. B., Reid A. M. Expression of the mouse HPRT gene: deletional analysis of the promoter region of an X-chromosome linked housekeeping gene. Cell. 1986 Jan 31;44(2):319–328. doi: 10.1016/0092-8674(86)90766-x. [DOI] [PubMed] [Google Scholar]
  18. Mitchell P. J., Carothers A. M., Han J. H., Harding J. D., Kas E., Venolia L., Chasin L. A. Multiple transcription start sites, DNase I-hypersensitive sites, and an opposite-strand exon in the 5' region of the CHO dhfr gene. Mol Cell Biol. 1986 Feb;6(2):425–440. doi: 10.1128/mcb.6.2.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reynolds G. A., Basu S. K., Osborne T. F., Chin D. J., Gil G., Brown M. S., Goldstein J. L., Luskey K. L. HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions. Cell. 1984 Aug;38(1):275–285. doi: 10.1016/0092-8674(84)90549-x. [DOI] [PubMed] [Google Scholar]
  21. Saffer J. D., Singer M. F. Transcription from SV 40-like monkey DNA sequences. Nucleic Acids Res. 1984 Jun 11;12(11):4769–4788. doi: 10.1093/nar/12.11.4769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Sharp P. A. Speculations on RNA splicing. Cell. 1981 Mar;23(3):643–646. doi: 10.1016/0092-8674(81)90425-6. [DOI] [PubMed] [Google Scholar]
  24. Stein R., Sciaky-Gallili N., Razin A., Cedar H. Pattern of methylation of two genes coding for housekeeping functions. Proc Natl Acad Sci U S A. 1983 May;80(9):2422–2426. doi: 10.1073/pnas.80.9.2422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Strohman R. C., Moss P. S., Micou-Eastwood J., Spector D., Przybyla A., Paterson B. Messenger RNA for myosin polypeptides: isolation from single myogenic cell cultures. Cell. 1977 Feb;10(2):265–273. doi: 10.1016/0092-8674(77)90220-3. [DOI] [PubMed] [Google Scholar]
  26. Toniolo D., D'Urso M., Martini G., Persico M., Tufano V., Battistuzzi G., Luzzatto L. Specific methylation pattern at the 3' end of the human housekeeping gene for glucose 6-phosphate dehydrogenase. EMBO J. 1984 Sep;3(9):1987–1995. doi: 10.1002/j.1460-2075.1984.tb02080.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tykocinski M. L., Max E. E. CG dinucleotide clusters in MHC genes and in 5' demethylated genes. Nucleic Acids Res. 1984 May 25;12(10):4385–4396. doi: 10.1093/nar/12.10.4385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Williams T. J., Fried M. The MES-1 murine enhancer element is closely associated with the heterogeneous 5' ends of two divergent transcription units. Mol Cell Biol. 1986 Dec;6(12):4558–4569. doi: 10.1128/mcb.6.12.4558. [DOI] [PMC free article] [PubMed] [Google Scholar]

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