Methylation changes in the apolipoprotein AI gene during embryonic development of the mouse

Ruth Shemer, Tal Kafri, Anita O'Connell, Shlomo Eisenberg, Jan L. Breslow, Aharon Razin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

We report here a detailed study of developmental changes in the methylation status of specific sites in a single-copy tissue-specific gene, from the germ cell through the early embryo to adult tissues. Two sites at the 5′ end of the mouse apolipoprotein AI gene were unmethylated in the ovulated unfertilized oocytes and methylated in the sperm. In contrast, a third site, located upstream of the gene, was methylated and a CpG island within the gene was unmethylated in both oocyte and sperm. The methylated sites, regardless of maternal or paternal origin, underwent dentethylation in the early embryo (8-16 cells) and stayed unmethylated through the late blastocyst stage. During gastrulation, non-CpG island sites underwent methylation, followed by gradual demethylation at specific sites in tissues parallel to expression of the gene (liver and intestine). The formation of the mature tissue-specific methylation pattern of the apolipoprotein AI gene, therefore, involves the following three major events: (i) erasure of the germ-cell methylation pattern (at the 8- to 16-cell stage), (ii) formation of a new methylation pattern by de novo methylation of non-CpG island sites (during gastrulation), and (iii) tissue-specific demethylation associated with the onset of expression of the gene.

Original languageAmerican English
Pages (from-to)11300-11304
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number24
StatePublished - 1991

Keywords

  • CpG island
  • Human apolipoprotein AI transgene
  • Polymerase chain reaction
  • Tissue-specific methylation

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