Li X, Gray S G, Flam F, Pietsch T, Ekström T J
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
Int J Dev Biol. 1998 Jul;42(5):687-93.
We have previously shown that the four promoters of the IGF2 gene are under a tight but dynamic control during human liver development, whereby P3 and P1 are reciprocally active before and after birth respectively while the P2 and P4 promoters are constitutively active at a relatively lower level. In this study, we investigated the methylation status of the promoters P1 and P3 of IGF2 and the promoter region of the H19 gene in developing human livers ranging from fetal to late adult. A region of about 300 bp immediately upstream of the IGF2 exon 5 was found to be subjected to a developmental-specific methylation and this may correlate to the P3 promoter activity. The P1 domain of IGF2 was also found to be methylated in a developmentally-specific pattern. The promoter region of the H19 gene displayed different methylation patterns in different development stages showing decreased general methylation with increase of age. Therefore, regional- and developmental-specific DNA methylation is displayed in the promoter regions of the IGF2 and H19 genes. This may be an important factor involved in gene regulation in the developing human liver.
我们之前已经表明，IGF2基因的四个启动子在人类肝脏发育过程中受到严格但动态的调控，其中P3和P1分别在出生前后相互激活，而P2和P4启动子在相对较低水平上持续活跃。在本研究中，我们调查了从胎儿到成年晚期的发育中的人类肝脏中IGF2的P1和P3启动子以及H19基因启动子区域的甲基化状态。发现IGF2外显子5上游紧邻的约300 bp区域经历了发育特异性甲基化，这可能与P3启动子活性相关。还发现IGF2的P1结构域以发育特异性模式发生甲基化。H19基因的启动子区域在不同发育阶段表现出不同的甲基化模式，总体甲基化随着年龄增长而降低。因此，IGF2和H19基因的启动子区域呈现出区域特异性和发育特异性的DNA甲基化。这可能是参与人类发育肝脏基因调控的一个重要因素。
