Programmed demethylation in CpG islands during human fetal development

Barbara R. Migeon, Mitchell M. Holland, Daniel J. Driscoll, J. Courtland Robinson

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


The mechanism for establishing the DNA methylation patterns observed in adult mammalian tissues is not well understood. To determine when adult patterns are established for housekeeping genes, we examined the clustered CpGs in genes on the human active X chromosome (PGK, G6PD, P3, GdX, HPRT) and the autosomal gene, DHFR. We find unique methylation patterns present at the P3 locus in all tissues analyzed from 6- to 9-week fetal specimens, and at the HPRT locus in adrenal gland DNA at this stage of development. Adult patterns are established subsequently by demethylating specific CpGs. Our results show that demethylating events affecting CpG islands are programmed during mammalian fetal development. They suggest that the process of de novo methylation in the fetus methylates at least some sites in the 3′ region of the CpG islands in active genes and that adult patterns are established at 6-14 weeks developmental age by sequence-specific demethylation.

Original languageEnglish (US)
Pages (from-to)159-168
Number of pages10
JournalSomatic Cell and Molecular Genetics
Issue number2
StatePublished - Mar 1991

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology


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