Hypoxia-induced alterations of transcriptome and chromatin accessibility in HL-1 cells.

Abstract

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.