Wang Hao, Huang Ning, Liu Yuqi, Cang Jing, Xue Zhanggang
a Department of Anesthesiology , Zhongshan Hospital, Shanghai Medical College of Fudan University , Shanghai , P.R. China.
Ren Fail. 2016 Jul;38(6):982-8. doi: 10.3109/0886022X.2016.1172973. Epub 2016 Apr 21.
Ten-Eleven Translocation (TET) proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytonsie (5hmC). Our recent work found a decline in global 5hmC level in mouse kidney insulted by ischemia reperfusion (IR). However, the genomic distribution of 5hmC in mouse kidney and its relationship with gene expression remain elusive. Here, we profiled the DNA hydroxymethylome of mouse kidney by hMeDIP-seq and revealed that 5hmC is enriched in genic regions but depleted from intergenic regions. Correlation analyses showed that 5hmC enrichment in gene body is positively associated with gene expression level in mouse kidney. Moreover, IR injury-associated genes (both up- and down-regulated genes during renal IR injury) in mouse kidney exhibit significantly higher 5hmC enrichment in their gene body regions when compared to those un-changed genes. Collectively, our study not only provides the first DNA hydroxymethylome of kidney tissues but also suggests that DNA hyper-hydroxymethylation in gene body may be a novel epigenetic marker of IR injury-associated genes.
十一易位（TET）蛋白将5-甲基胞嘧啶（5mC）氧化为5-羟甲基胞嘧啶（5hmC）。我们最近的研究发现，缺血再灌注（IR）损伤的小鼠肾脏中整体5hmC水平下降。然而，5hmC在小鼠肾脏中的基因组分布及其与基因表达的关系仍不清楚。在这里，我们通过hMeDIP-seq对小鼠肾脏的DNA羟甲基化组进行了分析，发现5hmC在基因区域富集，但在基因间区域缺失。相关性分析表明，基因体内的5hmC富集与小鼠肾脏中的基因表达水平呈正相关。此外，与未改变的基因相比，小鼠肾脏中IR损伤相关基因（肾脏IR损伤期间上调和下调的基因）在其基因体区域表现出显著更高的5hmC富集。总之，我们的研究不仅提供了首个肾脏组织的DNA羟甲基化组，还表明基因体中的DNA高羟甲基化可能是IR损伤相关基因的一种新的表观遗传标记。
