Tissue-Specific Hypomethylation and Expression of Rat Phosphoenolpyruvate Carboxykinase Gene Induced by in Vivo Treatment of Fetuses and Neonates with 5-Azacytidine

Nissim Benvenisty, David Menchei, Moshe Szyf, Aharon Razin, Lea Reshef

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Rat fetuses of 17-19-day gestation were injected in utero with 5-azacytidine (two to three daily injections of 40 μg/fetus). Neonates were injected with seven daily injections (1 mg/kg). DNA samples were isolated from the fetal and neonatal livers and neonatal spleen and subjected to analysis of their methylation status. Overall methylation was analyzed by the nearest-neighbor analysis (at CpG sites) and the pattern of methylation at CCGG sites by Southern blot analysis using phosphoenolpyruvate carboxykinase (PEPCK) sequences as probes. While DNAs from the liver and spleen undergo hypomethylation to the same extent in response to the 5-azacytidine treatment, the changes in the methylation patterns of the PEPCK gene in the two tissues are strikingly different. The changes observed indicate that a decrease in the methylase activity (inhibition by 5-azacytidine) results in site- and tissue-specific hypomethylation. The tissue-specific changes in the methylation pattern are associated with a tissue-specific expression of the PEPCK gene. Although the gene is hypomethylated by azacytidine in both liver and spleen, it is expressed only in the liver. The expression of already active genes (PEPCK in the kidney and albumin in the liver) is not further enhanced by the drug.

Original languageEnglish
Pages (from-to)5015-5019
Number of pages5
JournalBiochemistry
Volume24
Issue number19
DOIs
StatePublished - 1 Sep 1985

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