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. 1988 Oct 25;16(20):9527–9543. doi: 10.1093/nar/16.20.9527

CpG islands of the X chromosome are gene associated.

M Alcalay 1, D Toniolo 1
PMCID: PMC338761  PMID: 3186440

Abstract

Unmethylated CpG rich islands are a feature of vertebrate DNA: they are associated with housekeeping and many tissue specific genes. CpG islands on the active X chromosome of mammals are also unmethylated. However, islands on the inactive X chromosome are heavily methylated. We have identified a CpG island in the 5' region of the G6PD gene, and two islands forty Kb 3' from the G6PD gene, on the human X chromosome. Expression of the G6PD gene is associated with concordant demethylation of all three CpG islands. We have shown that one of the two islands is in the promoter region of a housekeeping gene, GdX. In this paper we show that the second CpG island is also associated with a gene, P3. The P3 gene has no homology to previously described genes. It is a single copy, 4 kb gene, conserved in evolution, and it has the features of a housekeeping two genes is within the CpG island and that sequences in the islands have promoter function.

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Selected References

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

  1. Andrews P. W. Retinoic acid induces neuronal differentiation of a cloned human embryonal carcinoma cell line in vitro. Dev Biol. 1984 Jun;103(2):285–293. doi: 10.1016/0012-1606(84)90316-6. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  4. Collins S. J., Gallo R. C., Gallagher R. E. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. doi: 10.1038/270347a0. [DOI] [PubMed] [Google Scholar]
  5. Gardiner-Garden M., Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261–282. doi: 10.1016/0022-2836(87)90689-9. [DOI] [PubMed] [Google Scholar]
  6. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hattori M., Hidaka S., Sakaki Y. Sequence analysis of a KpnI family member near the 3' end of human beta-globin gene. Nucleic Acids Res. 1985 Nov 11;13(21):7813–7827. doi: 10.1093/nar/13.21.7813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kohler P. O., Bridson W. E. Isolation of hormone-producing clonal lines of human choriocarcinoma. J Clin Endocrinol Metab. 1971 May;32(5):683–687. doi: 10.1210/jcem-32-5-683. [DOI] [PubMed] [Google Scholar]
  9. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  10. Lavia P., Macleod D., Bird A. Coincident start sites for divergent transcripts at a randomly selected CpG-rich island of mouse. EMBO J. 1987 Sep;6(9):2773–2779. doi: 10.1002/j.1460-2075.1987.tb02572.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lindsay S., Monk M., Holliday R., Huschtscha L., Davies K. E., Riggs A. D., Flavell R. A. Differences in methylation on the active and inactive human X chromosomes. Ann Hum Genet. 1985 May;49(Pt 2):115–127. doi: 10.1111/j.1469-1809.1985.tb01683.x. [DOI] [PubMed] [Google Scholar]
  12. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Persico M. G., Viglietto G., Martini G., Toniolo D., Paonessa G., Moscatelli C., Dono R., Vulliamy T., Luzzatto L., D'Urso M. Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: primary structure of the protein and unusual 5' non-coding region. Nucleic Acids Res. 1986 Mar 25;14(6):2511–2522. doi: 10.1093/nar/14.6.2511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Reik W., Collick A., Norris M. L., Barton S. C., Surani M. A. Genomic imprinting determines methylation of parental alleles in transgenic mice. Nature. 1987 Jul 16;328(6127):248–251. doi: 10.1038/328248a0. [DOI] [PubMed] [Google Scholar]
  16. Rosenthal N. Identification of regulatory elements of cloned genes with functional assays. Methods Enzymol. 1987;152:704–720. doi: 10.1016/0076-6879(87)52075-4. [DOI] [PubMed] [Google Scholar]
  17. Sapienza C., Peterson A. C., Rossant J., Balling R. Degree of methylation of transgenes is dependent on gamete of origin. Nature. 1987 Jul 16;328(6127):251–254. doi: 10.1038/328251a0. [DOI] [PubMed] [Google Scholar]
  18. Skowronski J., Singer M. F. Expression of a cytoplasmic LINE-1 transcript is regulated in a human teratocarcinoma cell line. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6050–6054. doi: 10.1073/pnas.82.18.6050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Swain J. L., Stewart T. A., Leder P. Parental legacy determines methylation and expression of an autosomal transgene: a molecular mechanism for parental imprinting. Cell. 1987 Aug 28;50(5):719–727. doi: 10.1016/0092-8674(87)90330-8. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Toniolo D., Martini G., Migeon B. R., Dono R. Expression of the G6PD locus on the human X chromosome is associated with demethylation of three CpG islands within 100 kb of DNA. EMBO J. 1988 Feb;7(2):401–406. doi: 10.1002/j.1460-2075.1988.tb02827.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Toniolo D., Persico M., Alcalay M. A "housekeeping" gene on the X chromosome encodes a protein similar to ubiquitin. Proc Natl Acad Sci U S A. 1988 Feb;85(3):851–855. doi: 10.1073/pnas.85.3.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wolf S. F., Dintzis S., Toniolo D., Persico G., Lunnen K. D., Axelman J., Migeon B. R. Complete concordance between glucose-6-phosphate dehydrogenase activity and hypomethylation of 3' CpG clusters: implications for X chromosome dosage compensation. Nucleic Acids Res. 1984 Dec 21;12(24):9333–9348. doi: 10.1093/nar/12.24.9333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wolf S. F., Migeon B. R. Clusters of CpG dinucleotides implicated by nuclease hypersensitivity as control elements of housekeeping genes. Nature. 1985 Apr 4;314(6010):467–469. doi: 10.1038/314467a0. [DOI] [PubMed] [Google Scholar]
  25. Yen P. H., Patel P., Chinault A. C., Mohandas T., Shapiro L. J. Differential methylation of hypoxanthine phosphoribosyltransferase genes on active and inactive human X chromosomes. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1759–1763. doi: 10.1073/pnas.81.6.1759. [DOI] [PMC free article] [PubMed] [Google Scholar]

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