DEVELOPMENTAL CONTROL OF ARGININOSUCCINATE LYASE GENE BY METHYLATION

The gene of argininosuccinate lyase (ASL) is expressed in a developmen tal specific manner in the liver and is regulated by hormones, namely glucocorticoids, glucagon and insulin, To assess the role of DNA methy lation in the developmental pattern of ASL gene expression, we analyze d the restriction profile obtained by cleavage of genomic DNA with Msp I and HpaII in fetal and adult rat liver, two developmental stages wit h different levels of expression of the ASL gene, Southern analysis sh owed that the 5' region of this gene appeared more methylated in the f etal liver which expressed ASL at a low level than in the adult liver where the ASL gene is highly expressed, Moreover, treatment of fetuses of various gestational stages with the hypomethylating agent 5-azacyt idine for 18 h caused an increase of the hepatic ASL activity and mRNA level, The stimulating effect of this drug could be also observed in vitro in cultured fetal hepatocytes. These results suggest a developme ntal control of the ASL gene by the DNA methylation status.