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Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression
Myocardial infarction (MI) is one of the deadliest diseases in the world, and the changes at the molecular level after MI and the DNA methylation features are not clear. Understanding the molecular characteristics of the early stages of MI is of significance for the treatment of the disease. In this...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263976/ https://www.ncbi.nlm.nih.gov/pubmed/35811717 http://dx.doi.org/10.3389/fcvm.2022.912454 |
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author | Han, Yuru Duan, Baoyu Wu, Jing Zheng, Yanjun Gu, Yinchen Cai, Xiaomeng Lu, Changlian Wu, Xubo Li, Yanfei Gu, Xuefeng |
author_facet | Han, Yuru Duan, Baoyu Wu, Jing Zheng, Yanjun Gu, Yinchen Cai, Xiaomeng Lu, Changlian Wu, Xubo Li, Yanfei Gu, Xuefeng |
author_sort | Han, Yuru |
collection | PubMed |
description | Myocardial infarction (MI) is one of the deadliest diseases in the world, and the changes at the molecular level after MI and the DNA methylation features are not clear. Understanding the molecular characteristics of the early stages of MI is of significance for the treatment of the disease. In this study, RNA-seq and MeDIP-seq were performed on heart tissue from mouse models at multiple time points (0 h, 10 min, 1, 6, 24, and 72 h) to explore genetic and epigenetic features that influence MI progression. Analysis based on a single point in time, the number of differentially expressed genes (DEGs) and differentially methylated regions (DMRs) increased with the time of myocardial infarction, using 0 h as a control group. Moreover, within 10 min of MI onset, the cells are mainly in immune response, and as the duration of MI increases, apoptosis begins to occur. Analysis based on time series data, the expression of 1012 genes was specifically downregulated, and these genes were associated with energy metabolism. The expression of 5806 genes was specifically upregulated, and these genes were associated with immune regulation, inflammation and apoptosis. Fourteen transcription factors were identified in the genes involved in apoptosis and inflammation, which may be potential drug targets. Analysis based on MeDIP-seq combined with RNA-seq methodology, focused on methylation at the promoter region. GO revealed that the downregulated genes with hypermethylation at 72 h were enriched in biological processes such as cardiac muscle contraction. In addition, the upregulated genes with hypomethylation at 72 h were enriched in biological processes, such as cell-cell adhesion, regulation of the apoptotic signaling pathway and regulation of angiogenesis. Among these genes, the Tnni3 gene was also present in the downregulated model. Hypermethylation of Tnni3 at 72 h after MI may be an important cause of exacerbation of MI. |
format | Online Article Text |
id | pubmed-9263976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92639762022-07-09 Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression Han, Yuru Duan, Baoyu Wu, Jing Zheng, Yanjun Gu, Yinchen Cai, Xiaomeng Lu, Changlian Wu, Xubo Li, Yanfei Gu, Xuefeng Front Cardiovasc Med Cardiovascular Medicine Myocardial infarction (MI) is one of the deadliest diseases in the world, and the changes at the molecular level after MI and the DNA methylation features are not clear. Understanding the molecular characteristics of the early stages of MI is of significance for the treatment of the disease. In this study, RNA-seq and MeDIP-seq were performed on heart tissue from mouse models at multiple time points (0 h, 10 min, 1, 6, 24, and 72 h) to explore genetic and epigenetic features that influence MI progression. Analysis based on a single point in time, the number of differentially expressed genes (DEGs) and differentially methylated regions (DMRs) increased with the time of myocardial infarction, using 0 h as a control group. Moreover, within 10 min of MI onset, the cells are mainly in immune response, and as the duration of MI increases, apoptosis begins to occur. Analysis based on time series data, the expression of 1012 genes was specifically downregulated, and these genes were associated with energy metabolism. The expression of 5806 genes was specifically upregulated, and these genes were associated with immune regulation, inflammation and apoptosis. Fourteen transcription factors were identified in the genes involved in apoptosis and inflammation, which may be potential drug targets. Analysis based on MeDIP-seq combined with RNA-seq methodology, focused on methylation at the promoter region. GO revealed that the downregulated genes with hypermethylation at 72 h were enriched in biological processes such as cardiac muscle contraction. In addition, the upregulated genes with hypomethylation at 72 h were enriched in biological processes, such as cell-cell adhesion, regulation of the apoptotic signaling pathway and regulation of angiogenesis. Among these genes, the Tnni3 gene was also present in the downregulated model. Hypermethylation of Tnni3 at 72 h after MI may be an important cause of exacerbation of MI. Frontiers Media S.A. 2022-06-24 /pmc/articles/PMC9263976/ /pubmed/35811717 http://dx.doi.org/10.3389/fcvm.2022.912454 Text en Copyright © 2022 Han, Duan, Wu, Zheng, Gu, Cai, Lu, Wu, Li and Gu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Han, Yuru Duan, Baoyu Wu, Jing Zheng, Yanjun Gu, Yinchen Cai, Xiaomeng Lu, Changlian Wu, Xubo Li, Yanfei Gu, Xuefeng Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression |
title | Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression |
title_full | Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression |
title_fullStr | Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression |
title_full_unstemmed | Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression |
title_short | Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression |
title_sort | analysis of time series gene expression and dna methylation reveals the molecular features of myocardial infarction progression |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263976/ https://www.ncbi.nlm.nih.gov/pubmed/35811717 http://dx.doi.org/10.3389/fcvm.2022.912454 |
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