胚胎肺细胞中基因的甲基化及其对基因表达的影响。
Methylation of and genes in embryonic lung cells and their impact on gene expression.
作者信息
Chen Ying, Wang Jinke, Wang Xin, Liu Yingxun, Gu Bing, Zhao Guodong, Li Ying
机构信息
School of Medical Technology, Xuzhou Medical University, Xuzhou 221004, China.
State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China.
出版信息
Ann Transl Med. 2018 Dec;6(23):459. doi: 10.21037/atm.2018.11.57.
BACKGROUND
During embryonic development, epigenetics plays an irreplaceable role in maintaining the normal life activities of mammals. The study of methylation during embryonic lung development will gain a better understanding of the pathogenesis of lung disease. This study aimed to investigate the methylation of promoter-related CpG islands of and genes in human embryonic lung cells and their effects on the regulation of gene expression.
METHODS
The analyses of the methylation-prone region and the relationship with transcription factor binding sites were done by bioinformatic prediction. The bisulfite sequencing PCR was conducted aiming to the target areas. The methylation in promoter area and its impact on transcription factor binding as well as gene expression regulation effect were investigated by methylation inhibitor treatment and real-time PCR detection.
RESULTS
Bisulfite sequencing results showed that the CpG methylation predicted by bioinformatic prediction were in part agree with the bisulfite sequencing results, some of the CpG methylation were appeared in the important transcription factor binding sites. After treating with methylation inhibitors, the transcription of was significantly increased compared with , indicating that partial methylation in proximal promoter of had a certain effect on transcription Inhibition.
CONCLUSIONS
The methylation of genes had effect on the growth and development of the embryo in the embryonic lung development, which may be influenced by the combination of key transcription factors, thereby inhibiting the transcriptional expression, ultimately affected the expression and regulation of key genes. These results will help to further understand the epigenetic regulation and its impact on the embryonic development.
背景
在胚胎发育过程中，表观遗传学在维持哺乳动物正常生命活动中发挥着不可替代的作用。研究胚胎肺发育过程中的甲基化将有助于更好地理解肺部疾病的发病机制。本研究旨在探讨人胚胎肺细胞中 和 基因启动子相关CpG岛的甲基化情况及其对基因表达调控的影响。
方法
通过生物信息学预测对甲基化倾向区域及其与转录因子结合位点的关系进行分析。针对目标区域进行亚硫酸氢盐测序PCR。通过甲基化抑制剂处理和实时PCR检测，研究启动子区域的甲基化及其对转录因子结合的影响以及基因表达调控效应。
结果
亚硫酸氢盐测序结果显示，生物信息学预测的CpG甲基化部分与亚硫酸氢盐测序结果一致，部分CpG甲基化出现在重要的转录因子结合位点。用甲基化抑制剂处理后， 的转录与 相比显著增加，表明 近端启动子的部分甲基化对转录抑制有一定作用。
结论
基因的甲基化在胚胎肺发育过程中对胚胎的生长发育有影响，可能受关键转录因子结合的影响，从而抑制转录表达，最终影响关键基因的表达和调控。这些结果将有助于进一步了解表观遗传调控及其对胚胎发育的影响。
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