DNA 甲基化与转录组关联揭示心力衰竭的表观遗传病因。
Association of DNA methylation and transcriptome reveals epigenetic etiology of heart failure.
机构信息
Key Laboratory of Molecular Target and Clinical Pharmacology and National Key Laboratory of Respiratory Diseases, School of Pharmaceutic Sciences and Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
China State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
出版信息
Funct Integr Genomics. 2022 Feb;22(1):89-112. doi: 10.1007/s10142-021-00813-9. Epub 2021 Dec 6.
Epigenetic modifications viz. DNA methylation, histone modifications, and RNA-based alterations play a crucial role in the development of cardiovascular diseases. In this study, we investigated DNA methylation with an aim to reveal the epigenetic etiology of heart failure. Sprague-Dawley rats surviving myocardial infarction developed acute heart failure in 1 week. Genomic DNA methylation changes were profiled by bisulfite sequencing, and gene expression levels were analyzed by RNA-seq in failing and sham-operation hearts. A total of 3480 differentially methylated genes in the promoter regions including transcriptional start site and 1934 transcriptome-altered genes were identified in the defected hearts. Common differential genes were enriched by the gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction for HF phenotypes. Among these, Mettl11b, HDAC3, HDAC11, ubiquitination-related genes, and snoRNAs are new epigenetic classifiers that had not been reported yet, which may be important regulators in HF.
表观遗传修饰，如 DNA 甲基化、组蛋白修饰和基于 RNA 的改变，在心血管疾病的发展中起着至关重要的作用。在这项研究中，我们研究了 DNA 甲基化，旨在揭示心力衰竭的表观遗传病因。幸存心肌梗死的斯普拉格-道利大鼠在 1 周内发展为急性心力衰竭。通过亚硫酸氢盐测序对基因组 DNA 甲基化变化进行了分析，并通过 RNA-seq 对衰竭和假手术心脏中的基因表达水平进行了分析。在缺陷心脏中鉴定出了 3480 个在启动子区域（包括转录起始位点）中差异甲基化的基因和 1934 个转录组改变的基因。通过基因本体、京都基因与基因组百科全书通路和蛋白质-蛋白质相互作用对 HF 表型进行了共同差异基因的富集。其中，Mettl11b、HDAC3、HDAC11、泛素化相关基因和 snoRNAs 是尚未报道的新的表观遗传分类器，它们可能是 HF 的重要调节剂。
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