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Nucleic Acids Research, 1984, Vol. 12, No. 24 9333-9348
© 1984

MOLECULAR BIOLOGY

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

Stanley F. Wolf*, Suzanne Dintzis, Daniela Toniolo1, Graziella Persico1, Keith D. Lunnen, Joyce Axelman and Barbara R. Migeon+

Department of Pediatrics, Johns Hopkins University School of Medicine Baltimore, MD 21205, USA 1Istituto Internazionale di Genetic e Biofisica Via G. Marconi, 10, Napoli 80125, Italy

+To whom correspondence should be addressed

Received September 26, 1984. Revised November 21, 1984. Accepted November 21, 1984.

To explore the molecular basis of X chromosome inactivation, we have examined the human locus for glucose-6-phosphate dehydrogenase (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.

*Present address: Genetics Institute, 225 Longwood Avenue, Boston, MA 02115, USA


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