Renouf S, Fairand A, Husson A
Groupe de Biochimie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides No. 23, Faculté de Médecine-Pharmacie de Rouen, St. Etienne du Rouvray, France.
Biol Neonate. 1998;73(3):190-7. doi: 10.1159/000013977.
The gene of argininosuccinate lyase (ASL) is expressed in a developmental specific manner in the liver and is regulated by hormones, namely glucocorticoids, glucagon and insulin. To assess the role of DNA methylation in the developmental pattern of ASL gene expression, we analyzed the restriction profile obtained by cleavage of genomic DNA with MspI and HpaII in fetal and adult rat liver, two developmental stages with different levels of expression of the ASL gene. Southern analysis showed that the 5' region of this gene appeared more methylated in the fetal 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-azacytidine 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 developmental control of the ASL gene by the DNA methylation status.
精氨琥珀酸裂解酶（ASL）基因在肝脏中以发育特异性方式表达，并受激素调节，即糖皮质激素、胰高血糖素和胰岛素。为了评估DNA甲基化在ASL基因表达发育模式中的作用，我们分析了用MspI和HpaII切割胎儿和成年大鼠肝脏基因组DNA所获得的限制性图谱，这是ASL基因表达水平不同的两个发育阶段。Southern分析表明，该基因的5'区域在低水平表达ASL的胎儿肝脏中比在ASL基因高表达的成年肝脏中甲基化程度更高。此外，用去甲基化剂5-氮杂胞苷处理不同妊娠阶段的胎儿18小时，可导致肝脏ASL活性和mRNA水平升高。在培养的胎儿肝细胞中体外也可观察到这种药物的刺激作用。这些结果表明DNA甲基化状态对ASL基因有发育调控作用。
