Fig. 8

Reduction of repressive H3K27me3 marks by HMGA1 in mouse BZ CMs. a, Schematic overview of experiments (a,b) and representative image of immunofluorescent staining against H3K27me3, HMGA1-HA, phalloidin and DAPI on 14-dpi mouse hearts transduced with AAV9(CMV:HA-Hmga1). Dashed line indicates the injury border. Arrowheads indicate HMGA1-HA transduced CMs; asterisks indicate non-transduced CMs. Scale bar, 5 μm. b, Quantification of H3K27me3 signal intensity in single CMs in the BZ and RZ of 14-dpi Hmga1 (n = 4) and GFP (n = 4) virus transduced hearts. Datapoints represent single CM nuclei measured. Error bars indicate mean ± s.d. Statistics were performed using a one-way ANOVA followed by Tukey’s multiple comparisons test and show a significant difference between HA+ BZ CMs and HA− BZ CMs (P = 0.0046). c, Schematic overview for bulk sortChIC on Hmga1 OE CMs (c–e). d, Quantification of H3K27me3 levels on all genes, comparing normalized read coverage in control versus Hmga1 OE BZ CMs. H3K27me3 levels (peak data on n = 21,937 genes) are significantly reduced on gene bodies (P < 0.0001) in Hmga1 OE BZ CMs. Center line indicates median; whiskers indicate 10th/90th percentiles. Statistics were performed using a two-tailed unpaired t-test. e, Genome tracks of orthologs to example genes in Fig. 6g that are significantly upregulated in 14-dpT hmga1a OE CMs and were found downstream of Hmga1a (modules 5–8 in the scRNA-seq). Tracks show reduced H3K27me3 levels on genes in Hmga1 OE BZ CMs.