动脉粥样硬化相关的 ANGPT 和 ANGPTL 基因的组织特异性表观遗传学。
Tissue-specific epigenetics of atherosclerosis-related ANGPT and ANGPTL genes.
机构信息
Center for Bioinformatics & Genomics, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Department of Mathematics, Tulane University, New Orleans, LA 70118, USA.
出版信息
Epigenomics. 2019 Feb;11(2):169-186. doi: 10.2217/epi-2018-0150. Epub 2019 Jan 28.
AIM
To understand tissue-specific regulation of angiopoietin/angiopoietin-like (ANGPT/ANGPTL) genes (especially the five genes embedded in introns of host genes) and their association with atherosclerosis.
METHODS
Transcription and epigenomic databases from various normal tissues were examined in the vicinity of ANGPT1, ANGPT2, ANGPTL1, ANGPTL2, ANGPTL3, ANGPTL4 and ANGPTL8.
RESULTS
We identified tissue-specific enhancer chromatin regions that are likely to regulate transcription of ANGPT/ANGPTL genes and were intragenic, intergenic or host gene-linked. In addition, we found atherosclerosis-linked differentially methylated regions associated with ANGPT2 and with sequences encoding miR-145, a microRNA that targets ANGPT2 mRNA in cancers.
CONCLUSION
Our findings implicate enhancers as major contributors to tissue-specific expression of ANGPT/ANGPTL genes, which play critical roles in angiogenesis, atherosclerosis, cancer, and inflammatory and metabolic diseases.
目的
了解血管生成素/血管生成素样（ANGPT/ANGPTL）基因（特别是嵌入宿主基因内含子中的五个基因）的组织特异性调节及其与动脉粥样硬化的关系。
方法
在 ANGPT1、ANGPT2、ANGPTL1、ANGPTL2、ANGPTL3、ANGPTL4 和 ANGPTL8 附近检查了来自各种正常组织的转录和表观基因组数据库。
结果
我们鉴定了可能调节 ANGPT/ANGPTL 基因转录的组织特异性增强子染色质区域，这些区域位于基因内、基因间或宿主基因连接。此外，我们发现与动脉粥样硬化相关的差异甲基化区域与 ANGPT2 相关，与编码 miR-145 的序列相关，miR-145 是一种在癌症中靶向 ANGPT2 mRNA 的 microRNA。
结论
我们的研究结果表明，增强子是 ANGPT/ANGPTL 基因组织特异性表达的主要贡献者，这些基因在血管生成、动脉粥样硬化、癌症以及炎症和代谢性疾病中发挥着关键作用。
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