1 Department of Burn and Plastic Surgery, 2nd Affiliated Hospital of Shantou University Medical College , Shantou, China .
2 Department of Infectious Diseases, 2nd Affiliated Hospital of Shantou University Medical College , Shantou, China .
DNA Cell Biol. 2018 Jun;37(6):560-573. doi: 10.1089/dna.2018.4141. Epub 2018 Apr 2.
Epithelial mesenchyme transformation (EMT) of the medial edge epithelium (MEE) is the crucial process during palatal fusion. This work is aimed to elucidate the enhancer regulatory mechanism by genome-wide DNA methylation analysis of EMT during palatal fusion. Over 800 million clean reads, 325 million enzyme reads, and 234 million mapping reads were generated. The mapping rate was 68.85-74.32%, which included differentially methylated 17299 CCGG sites and 2363 CCWGG sites (p < 0.05, logFC >1). Methylated sites in intron and intergenic regions were more compared to other regions of all DNA elements. GO and KEGG analysis indicated that differential methylation sites related to embryonic palatal fusion genes (HDAC4, TCF7L2, and PDGFRB) at the enhancer were located on CCWGG region of non-CpG islands. In addition, the results showed that the enhancer for HDAC4 was hypermethylated, whereas the enhancers for TCF7L2 and PDGFRB were hypomethylated. The methylation status of enhancer regions of HDAC4, PDGFRB, and TCF7L2, involved in the regulation of the EMT during palatal fusion, may enlighten the development of novel epigenetic biomarkers in the treatment of cleft palate.
内胚层间充质转化（EMT）是腭融合过程中的关键过程。本研究旨在通过腭融合过程中 EMT 的全基因组 DNA 甲基化分析来阐明增强子调控机制。生成了超过 8 亿个清洁读数、3.25 亿个酶读数和 2.34 亿个映射读数。映射率为 68.85-74.32%，包括差异甲基化的 17299 个 CCGG 位点和 2363 个 CCWGG 位点（p<0.05，logFC>1）。与所有 DNA 元件的其他区域相比，内含子和基因间区域的甲基化位点更多。GO 和 KEGG 分析表明，与胚胎腭融合基因（HDAC4、TCF7L2 和 PDGFRB）相关的差异甲基化位点位于非 CpG 岛的 CCWGG 区域的增强子上。此外，结果表明，HDAC4 的增强子呈高甲基化状态，而 TCF7L2 和 PDGFRB 的增强子呈低甲基化状态。HDAC4、PDGFRB 和 TCF7L2 的增强子区域的甲基化状态参与了腭融合过程中的 EMT 调节，这可能为治疗腭裂的新型表观遗传生物标志物的开发提供启示。
