Fig. 2: Histone lysine succinylation is increased in monocytes and activates the transcriptional activity of the inflammatory pathway-related genes post- myocardial infarction (MI).

a, b Immunoblot analysis and quantification of Pan Ksucc (global succinylation) level in monocytes sorted from bone marrow (a) and peripheral blood (b) of mice indicated days after MI (n = 3; one-way ANOVA followed by Bonferroni multiple comparisons test). c Immunofluorescence staining and quantification of the proportion of Pan Ksucc and F4/80 in cardiac tissues on Day 3 with sham operation or after MI (scale bar=50 μm; n = 6; two-tailed unpaired Student t test). d, e Immunoblots of the levels of H3K23succ (histone) in bone marrow monocytes on Day 1 (d) and circulating monocytes on Day 3 (e) sorted from MI mice (n = 3; two-tailed unpaired Student t test). The blots were derived from the same experiment and processed in parallel. Total histone H3 level was set as an internal reference. f Immunofluorescence staining and quantification of the proportion of H3K23succ and F4/80 in cardiac tissues on Day 3 with sham operation or after MI (scale bar=50 μm; n = 5; two-tailed unpaired Student t test). g Heatmaps of H3K23succ binding peaks in circulating monocytes from sham and MI mice. Color intensity reflects the relative read count. Genes exhibiting similar distribution patterns were subjected to clustering analysis using an algorithm, revealing the binding trends of histone succinylation modifications across all genes. h Bar graph showing the genomic distribution of differential H3K23succ peaks (MI vs sham) relative to the translation start site (TSS). i, j KEGG (i) and GO (j) analyses of upregulated genes with increased H3K23succ modification. Statistical significance was assessed using a two-sided hypergeometric test with Benjamini-Hochberg correction for multiple testing. k The GSEA pathways enriched in the MI mice. The indicative genes were enriched for Inflammatory response and Tnf-α signaling via nfκb, as defined by hallmarks. l The mRNA levels of H3K23succ-enriched inflammatory genes in sham and MI mice (n = 6; two-tailed unpaired Student t test). m ChIP–qPCR analysis of H3K23succ enrichment at the promoters of inflammatory genes in sham and MI mice (n = 4; two-tailed unpaired Student t test). Results are presented as the mean ± SD of independent replicates. DAPI 4ʹ,6-diamidino-2-phenylindole, GO Gene Ontology, KEGG Kyoto Encyclopedia of Genes and Genomes, GSEA gene set enrichment analysis, NES normalized enrichment score, ChIP chromatin immunoprecipitation, PCR polymerase chain reaction. Source data are provided as a Source Data file.