Hypoxia-induced alterations of transcriptome and chromatin accessibility inHL-1 cells
Hypoxia-induced alterations of transcriptome and chromatin accessibility inHL-1 cells
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DOI：
10.1002/iub.2297
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发表时间：
2020-04-29
期刊：
影响因子：
4.6
通讯作者：
Hu, Weina
中科院分区：
文献类型：
--
作者：
Wang, Jingru;Wang, Yang;Hu, Weina
心脏缺氧在各类心脏病中起着重要作用，缺氧治疗不当常导致心肌细胞损伤甚至死亡。转录组分析和开放染色质作图已被用作了解心脏病发展的有力工具，但在缺氧引起的心脏损伤中，基因表达和染色质可及性之间的相互作用尚未得到广泛研究。在本研究中，以 HL-1 心肌细胞为模型，我们对转录组和染色质可及性进行了时间分析，以显示心脏对缺氧（4 小时和 8 小时）和复氧（24 小时）的反应。通过 RNA-seq 和 ATAC-seq，我们在整个基因组中总共鉴定了 2,912 个差异表达基因和 3,004 个差异峰，并表明这些数据彼此吻合良好。对于缺氧相关基因，我们还发现其 ATAC-seq 信号与 mRNA 水平之间存在高度相关性，例如 VEGF、Angpt1、Slc2a1、Bnip3 和 Casp3，Pearson 相关性 >0.7。有趣的是，复氧24小时后，235个基因的表达水平仍然与对照中的对应基因存在显着差异，表明这些基因在复氧后需要更长的恢复时间。总之，我们的研究表明缺氧和复氧后转录组的变化与染色质可及性之间存在密切关系，强调了开放染色质分析在相关研究中的重要性。此外，这里描述的分子反应将成为未来更好地理解缺氧诱发心脏病机制的宝贵资源。
Cardiac hypoxia plays a significant role in various types of heart disease, and improper treatment of hypoxia often leads to myocardial cell damage or even death. Transcriptome profiling and open chromatin mapping have been used as powerful tools to understand the development of heart disease, but the interplay between gene expression and chromatin accessibility has not been extensively investigated in hypoxia-induced cardiac damage. In this study, with HL-1 cardiomyocytes as a model, we performed temporal profiling of transcriptome and chromatin accessibility to show the cardiac responses to hypoxia (for 4 and 8 hr) and reoxygenation (for 24 hr). With RNA-seq and ATAC-seq, we identified a total of 2,912 differentially expressed genes and 3,004 differential peaks across the whole genome and showed that these data were in good agreement with each other. For hypoxia-related genes, we also discovered high correlations between their ATAC-seq signals and mRNA levels, such as VEGF, Angpt1, Slc2a1, Bnip3, and Casp3 with Pearson correlations >0.7. Interestingly, after 24 hr reoxygenation, the expression levels of 235 genes were still significantly different from the counterparts in the control, suggesting that these genes need a longer recovery time after reoxygenation. In conclusion, our study shows the close relationship between alterations of transcriptome and chromatin accessibility after hypoxia exposure and reoxygenation, emphasizing the importance of open chromatin profiling in related studies. In addition, the profiled molecular responses here will be valuable resources for better understanding of the mechanisms responsible for hypoxia-induced heart disease in future.