Comparative analysis of genome-wide gene expression profiles in hearts of C57B/6J mice

The neonatal murine heart is able to regenerate after severe injury, however this capacity quickly diminishes within the first week of life. Since DNA methylation is one of epigenetic mechanisms that plays a crucial role in cell development and gene expression regulation, we explored the changes of DNA methylation and gene expression patterns which accompany the loss of the transient regenerative potential in the heart. We used MeDIP-chip approach in order to compare global DNA methylation profiles in the murine hearts at 1 day and 7 days after birth, as well as, in hearts of mice at the age of 2 and 8 weeks. The comparison exposed a number of DNA promoter regions significantly changing their DNA methylation status between these time-points. As the result a number of DMRs have been identified which show an overrepresentation of genes which are critical for proper heart maturation and muscle development. The methylome transition from d1 to d7 is characterized by the excess of gene regulatory regions which gain over those that lose DNA methylation, thus suggesting that a number of genes active at d1 are repressed at d7. 8 samples, each sample is a pool representing three animals

新生小鼠心脏在遭受严重损伤后具备再生能力，但该再生能力在出生后第一周内快速消退。由于DNA甲基化（DNA methylation）是在细胞发育与基因表达调控中发挥关键作用的表观遗传机制（epigenetic mechanisms）之一，本研究探究了伴随心脏暂时性再生潜能丧失过程中的DNA甲基化与基因表达模式变化。本研究采用甲基化DNA免疫沉淀芯片（MeDIP-chip）技术，对比了出生后1天、7天的小鼠心脏，以及2周龄、8周龄小鼠心脏的全基因组DNA甲基化谱。该对比分析发现了多个在上述时间节点间DNA甲基化状态发生显著变化的DNA启动子区域。最终，本研究鉴定出一批差异甲基化区域（DMRs），这类区域富集了对心脏正常成熟及肌肉发育至关重要的基因。出生后1天至7天的甲基化组（methylome）转变特征为：获得DNA甲基化的基因调控区域数量多于丢失甲基化的区域，这表明在出生后1天活跃的多个基因在出生后7天被转录抑制。本研究共设置8个样本，每个样本为3只小鼠的心脏组织混合池。