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. 1984 Dec 21;12(24):9333–9348. doi: 10.1093/nar/12.24.9333

Complete concordance between glucose-6-phosphate dehydrogenase activity and hypomethylation of 3' CpG clusters: implications for X chromosome dosage compensation.

S F Wolf, S Dintzis, D Toniolo, G Persico, K D Lunnen, J Axelman, B R Migeon
PMCID: PMC320465  PMID: 6514579

Abstract

To explore the molecular basis of X chromosome inactivation, we have examined the human locus for glucose-6-phosphate dehydro-genase (G6PD) in various human tissues. Studies of DNA from males and females and from somatic cell hybrids with active or inactive X chromosomes, show that two remarkably dense clusters of CpG dinucleotides in the 3' coding sequences are hypomethylated in active G6PD genes but extensively methylated in inactive ones. Reacquisition of G6PD activity, either spontaneous or induced by 5-azacytidine, is accompanied by demethylation of both clusters; however, the clusters remain methylated in reactivants that express HPRT but not G6PD. Our observations implicate these 3' CpG clusters in the transcription of G6PD and in maintenance of dosage compensation for X linked housekeeping genes.

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Selected References

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

  1. Bird A. P. DNA methylation--how important in gene control? Nature. 1984 Feb 9;307(5951):503–504. doi: 10.1038/307503a0. [DOI] [PubMed] [Google Scholar]
  2. Chen M. J., Shimada T., Moulton A. D., Cline A., Humphries R. K., Maizel J., Nienhuis A. W. The functional human dihydrofolate reductase gene. J Biol Chem. 1984 Mar 25;259(6):3933–3943. [PubMed] [Google Scholar]
  3. Gartler S. M., Riggs A. D. Mammalian X-chromosome inactivation. Annu Rev Genet. 1983;17:155–190. doi: 10.1146/annurev.ge.17.120183.001103. [DOI] [PubMed] [Google Scholar]
  4. Jabs E. W., Wolf S. F., Migeon B. R. Characterization of reiterated human DNA with respect to mammalian X chromosome homology. Somat Cell Mol Genet. 1984 Jan;10(1):93–103. doi: 10.1007/BF01534476. [DOI] [PubMed] [Google Scholar]
  5. Lyon M. F. X-chromosome inactivation and developmental patterns in mammals. Biol Rev Camb Philos Soc. 1972 Jan;47(1):1–35. doi: 10.1111/j.1469-185x.1972.tb00969.x. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Migeon B. R., Sprenkle J. A., Do T. T. Stability of the "two active X" phenotype in triploid somatic cells. Cell. 1979 Nov;18(3):637–641. doi: 10.1016/0092-8674(79)90118-1. [DOI] [PubMed] [Google Scholar]
  8. Migeon B. R., Wolf S. F., Mareni C., Axelman J. Derepression with decreased expression of the G6PD locus on the inactive X chromosome in normal human cells. Cell. 1982 Jun;29(2):595–600. doi: 10.1016/0092-8674(82)90175-1. [DOI] [PubMed] [Google Scholar]
  9. Mohandas T., Sparkes R. S., Shapiro L. J. Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation. Science. 1981 Jan 23;211(4480):393–396. doi: 10.1126/science.6164095. [DOI] [PubMed] [Google Scholar]
  10. Pai G. S., Sprenkle J. A., Do T. T., Mareni C. E., Migeon B. R. Localization of loci for hypoxanthine phosphoribosyltransferase and glucose-6-phosphate dehydrogenase and biochemical evidence of nonrandom X chromosome expression from studies of a human X-autosome translocation. Proc Natl Acad Sci U S A. 1980 May;77(5):2810–2813. doi: 10.1073/pnas.77.5.2810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Persico M. G., Toniolo D., Nobile C., D'Urso M., Luzzatto L. cDNA sequences of human glucose 6-phosphate dehydrogenase cloned in pBR322. Nature. 1981 Dec 24;294(5843):778–780. doi: 10.1038/294778a0. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Wolf S. F., Jolly D. J., Lunnen K. D., Friedmann T., Migeon B. R. Methylation of the hypoxanthine phosphoribosyltransferase locus on the human X chromosome: implications for X-chromosome inactivation. Proc Natl Acad Sci U S A. 1984 May;81(9):2806–2810. doi: 10.1073/pnas.81.9.2806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Wolf S. F., Mareni C. E., Migeon B. R. Isolation and characterization of cloned DNA sequences that hybridize to the human X chromosome. Cell. 1980 Aug;21(1):95–102. doi: 10.1016/0092-8674(80)90117-8. [DOI] [PubMed] [Google Scholar]
  16. Wolf S. F., Migeon B. R. Implications for X-chromosome regulation from studies of human X-chromosome DNA. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 2):621–630. doi: 10.1101/sqb.1983.047.01.073. [DOI] [PubMed] [Google Scholar]
  17. Wolf S. F., Migeon B. R. Studies of X chromosome DNA methylation in normal human cells. Nature. 1982 Feb 25;295(5851):667–671. doi: 10.1038/295667a0. [DOI] [PubMed] [Google Scholar]
  18. 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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