Co-effects of m6A and chromatin accessibility dynamics in the regulation of cardiomyocyte differentiation

Figures

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  Fig. 1. General features of m6A modification during cardiomyocyte differentiation. A Schematic overview of the study design. B Number of expressed genes and m6A-modifed genes detected at four stages during cardiomyocyte differentiation. C Distribution of m6A peaks on transcripts and enriched motifs during cardiomyocyte differentiation. D m6A levels (IP/input ratio) of four stages during cardiomyocyte differentiation. E m6A levels in different genetic regions during cardiomyocyte differentiation. D0, Day0; D2, Day2; D5, Day5, D10, Day10

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  Fig. 2. Dynamics of m6A during cardiomyocyte differentiation. A Heatmap of m6A level for each peak at four differentiation stages, clustered using k-means. B The percentages of m6A with changes (Fold Change > 1.2, red bar) and without changes (blue bar). Right: The peaks that show changes in m6A modification levels on the left are further subdivided into peaks that change once, twice and thrice. C Origin of m6A peaks at various stages during cardiomyocyte differentiation. D The genes related to stem cell maintenance obtained from the GO database were compared with the genes that showed m6A modifications. The p-value was calculated using a one-tailed hypergeometric test. (E) GO enrichment analysis results for the gene sets contained in cluster 8 in A. F Genome browser view of the m6A signal at four differentiation stages on RYR2 and MED21

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  Fig. 3. Dynamics of METTL14, RBM15, ALKBH5 during cardiomyocyte differentiation. A Dispersion score of expression levels of m6A writers and erasers during cardiomyocyte differentiation. B Changes in expression levels (blue line) and m6A modification levels (red line) of METTL14, RBM15, ALKBH5 during differentiation. The relative signal represents the change in the latter stage compared to the previous stage. C Distribution of the correlation between the m6A level of the transcriptome and the expression of METTL14, RBM15, and ALKBH5. PCC: Pearson correlation coefficient. D Identification of potential target genes of METTL14, RBM15, ALKBH5. m6A pos/neg cor gene: genes whose m6A levels are positively/negatively correlated with the expression of m6A-related proteins. Expression pos/neg cor gene: genes whose expression levels are positively/negatively correlated with the expression of m6A-related proteins. The p-value was calculated using one-tailed hypergeometric test. (E) GO enrichment analysis of potential target genes of METTL14, RBM15 and ALKBH5

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  Fig. 4. Relationship between chromatin accessibility and m6A-related proteins. A The accessibility of potential target genes of m6A-related proteins compared with the accessibility of all genes. Blue represents potential target genes, green represents random genes with same number as potential target genes and red represents all genes we detected. * represents p-value < 0.05 and ** represents p-value < 0.01. B Genes exhibiting various correlations between m6A level and the expression level of METTL14, RBM15 and ALKBH5 show similar accessibility. * represents p-value < 0.05. C Genes exhibiting various correlations between m6A level and the expression level of YTHDC2 and IGF2BP2 show similar accessibility. D Cumulative curve shows the m6A modification levels of genes displaying different correlations between m6A modification levels and expression levels of YTHDC2 and IGF2BP2. neg/not/pos cor: genes whose m6A level or accessibility are negatively/not/positively correlated with the expression of m6A-related proteins

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  Fig. 5. The relationship between the chromatin accessibility and m6A level. A Chromatin accessibility of genes with(red) and without(blue) m6A modification. * represents p-value < 0.05, Wilcoxon test. B Comparison of m6A levels in genes with varying chromatin accessibility. Genes were classified into three categories based on their chromatin accessibility: the top 10% of genes with high accessibility, the bottom 10% of genes with low accessibility, and the remaining genes with medium accessibility. * represents p-value < 0.05, Wilcoxon test. C Changes in m6A level and chromatin accessibility during differentiation, with colors indicating 5 gene categories (group 1 to group 5) based on their distinct patterns of changes. D GO enrichment analysis results for gene categories from Fig. 5C. E Relationship between the correlation of m6A levels and accessibility, and m6A level changes at various differentiation stages. Genes were ranked according to the PCC of their m6A levels with chromatin accessibility, and every 5% of genes were grouped without top 5% and bottom 5%. PCC: Pearson correlation coefficient. F Overlap of genes with only m6A change across different differentiation stages