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 Toniolo, Graziella Persico, Keith D. Lunnen, Joyce Axelman, Barbara R. Migeon

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9333-9348
Number of pages16
JournalNucleic acids research
Volume12
Issue number24
DOIs
StatePublished - Dec 21 1984

ASJC Scopus subject areas

  • Genetics

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