34 research outputs found
H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts
BACKGROUND: H3K27ac histone acetylome changes contribute to the phenotypic response in heart diseases, particularly in end-stage heart failure. However, such epigenetic alterations have not been systematically investigated in remodeled non-failing human hearts. Therefore, valuable insight into cardiac dysfunction in early remodeling is lacking. This study aimed to reveal the acetylation changes of chromatin regions in response to myocardial remodeling and their correlations to transcriptional changes of neighboring genes. RESULTS: We detected chromatin regions with differential acetylation activity (DARs; Padj. < 0.05) between remodeled non-failing patient hearts and healthy donor hearts. The acetylation level of the chromatin region correlated with its RNA polymerase II occupancy level and the mRNA expression level of its adjacent gene per sample. Annotated genes from DARs were enriched in disease-related pathways, including fibrosis and cell metabolism regulation. DARs that change in the same direction have a tendency to cluster together, suggesting the well-reorganized chromatin architecture that facilitates the interactions of regulatory domains in response to myocardial remodeling. We further show the differences between the acetylation level and the mRNA expression level of cell-type-specific markers for cardiomyocytes and 11 non-myocyte cell types. Notably, we identified transcriptome factor (TF) binding motifs that were enriched in DARs and defined TFs that were predicted to bind to these motifs. We further showed 64 genes coding for these TFs that were differentially expressed in remodeled myocardium when compared with controls. CONCLUSIONS: Our study reveals extensive novel insight on myocardial remodeling at the DNA regulatory level. Differences between the acetylation level and the transcriptional level of cell-type-specific markers suggest additional mechanism(s) between acetylome and transcriptome. By integrating these two layers of epigenetic profiles, we further provide promising TF-encoding genes that could serve as master regulators of myocardial remodeling. Combined, our findings highlight the important role of chromatin regulatory signatures in understanding disease etiology
Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine
[This corrects the article DOI: 10.1186/s13054-016-1208-6.]
Forty years of carabid beetle research in Europe - from taxonomy, biology, ecology and population studies to bioindication, habitat assessment and conservation
Volume: 100Start Page: 55End Page: 14
H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts
Background: H3K27ac histone acetylome changes contribute to the phenotypic response in heart diseases, particularly in end-stage heart failure. However, such epigenetic alterations have not been systematically investigated in remodeled non-failing human hearts. Therefore, valuable insight into cardiac dysfunction in early remodeling is lacking. This study aimed to reveal the acetylation changes of chromatin regions in response to myocardial remodeling and their correlations to transcriptional changes of neighboring genes. Results: We detected chromatin regions with differential acetylation activity (DARs; P adj. < 0.05) between remodeled non-failing patient hearts and healthy donor hearts. The acetylation level of the chromatin region correlated with its RNA polymerase II occupancy level and the mRNA expression level of its adjacent gene per sample. Annotated genes from DARs were enriched in disease-related pathways, including fibrosis and cell metabolism regulation. DARs that change in the same direction have a tendency to cluster together, suggesting the well-reorganized chromatin architecture that facilitates the interactions of regulatory domains in response to myocardial remodeling. We further show the differences between the acetylation level and the mRNA expression level of cell-type-specific markers for cardiomyocytes and 11 non-myocyte cell types. Notably, we identified transcriptome factor (TF) binding motifs that were enriched in DARs and defined TFs that were predicted to bind to these motifs. We further showed 64 genes coding for these TFs that were differentially expressed in remodeled myocardium when compared with controls. Conclusions: Our study reveals extensive novel insight on myocardial remodeling at the DNA regulatory level. Differences between the acetylation level and the transcriptional level of cell-type-specific markers suggest additional mechanism(s) between acetylome and transcriptome. By integrating these two layers of epigenetic profiles, we further provide promising TF-encoding genes that could serve as master regulators of myocardial remodeling. Combined, our findings highlight the important role of chromatin regulatory signatures in understanding disease etiology
Additional file 3 of H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts
Additional file 3. Supplementary Figure 3. Correlation plots between H3K27ac ChIP-seq (red) with RNAPII ChIP-seq (blue) and RNA-seq datasets (blue), respectively. Correlations in four control samples (from a to d) used in this study. Gene expression rank is based on RPKM values
Additional file 14 of H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts
Additional file 14. Supplementary Table 8. The chromatin acetylation changes and the mRNA expression changes of key regulators and targets in the Hippo pathway
Additional file 3 of H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts
Additional file 3. Supplementary Figure 3. Correlation plots between H3K27ac ChIP-seq (red) with RNAPII ChIP-seq (blue) and RNA-seq datasets (blue), respectively. Correlations in four control samples (from a to d) used in this study. Gene expression rank is based on RPKM values