Ono T, Takahashi N, Okada S
Radiation Biology Center, Kyoto University, Japan.
Mutat Res. 1989 Jan;219(1):39-50. doi: 10.1016/0921-8734(89)90039-8.
Age-associated changes in DNA structure and mRNA level were studied for the c-myc gene in spleen and liver of mice at 2, 14 and 26 months of age. Neither amplification nor rearrangement of the gene was detected in either tissue at any age. However, a significant alteration was observed in the methylation profile. The profile of the gene and its vicinity was determined using various methylation-sensitive restriction enzymes. In both tissues, the gene had an unmethylated domain ranging from -2 kb upstream of the 5' end of the first exon to the 3' end of the first intron. It was flanked by partially methylated regions, where age-dependent changes as well as tissue specificity were observed. In the spleen, age-related hypomethylation was observed at both the 3' and 5' sides of the domain. In contrast, hypermethylation was found in the liver only at the 3' side. The steady-state level of c-myc mRNA showed a drastic decrease in liver from youth to middle age, while splenic mRNA changed little. The correlation between the changes of mRNA and DNA methylation is discussed.
研究了2月龄、14月龄和26月龄小鼠脾脏和肝脏中c-myc基因的DNA结构和mRNA水平随年龄的变化。在任何年龄的任何组织中均未检测到该基因的扩增或重排。然而，观察到甲基化谱有显著改变。使用各种甲基化敏感限制酶确定了该基因及其附近区域的甲基化谱。在两种组织中，该基因都有一个未甲基化区域，范围从第一个外显子5'端上游-2 kb到第一个内含子的3'端。它两侧是部分甲基化区域，在这些区域观察到了年龄依赖性变化以及组织特异性。在脾脏中，在该区域的3'和5'侧均观察到与年龄相关的低甲基化。相反，仅在肝脏的3'侧发现高甲基化。c-myc mRNA的稳态水平在肝脏中从青年到中年急剧下降，而脾脏mRNA变化不大。讨论了mRNA变化与DNA甲基化之间的相关性。
