Fig. 4: Increased H3K9la promoted GRAMD1A transcription in KRAS mutant CRC. | Cell Death & Differentiation

Fig. 4: Increased H3K9la promoted GRAMD1A transcription in KRAS mutant CRC.

From: KRAS mutation increases histone H3 lysine 9 lactylation (H3K9la) to promote colorectal cancer progression by facilitating cholesterol transporter GRAMD1A expression

Fig. 4

A H3K9la correlated with steady-state mRNA levels. The average ChIP signal intensity (read count per million mapped reads) for indicated antibodies is shown for genes with different expression levels (the top 25%, the second 25%, the third 25%, and the bottom 25% of RNA-seq counts). B Distribution and level of H3K9la sites relative to translation start site (TSS) with or without LDH inhibitor oxamate treatment. C Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differential H3K9la peaks with or without oxamate treatment. D Bioinformatics analysis filtered GRAMD1A as a downstream target of H3K9la. E IGV tracks for GRAMD1A from H3K9la ChIP-seq analysis. F IGV tracks for GRAMD1A promoter region from H3K9la ChIP-seq and ATAC-seq analysis. G H3K9la levels at GRAMD1A promoter region by ChIP-qPCR assay and H GRAMD1A mRNA levels by qPCR of KRAS mutant and wild-type CRC tissues and normal colon tissues. n  =  3. I H3K9la levels at GRAMD1A promoter region by ChIP-qPCR assay, J GRAMD1A mRNA levels by qPCR and K luciferase activity by dual luciferase reporter assay of isogenic DLD1 cells harboring G13D mutant, wild-type or both alleles of KRAS treated with 10 mM oxamate and 10 mM Nala. n  =  3. Values are presented as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, determined by two-tailed Student’s t-test (G, H) and one-way ANOVA (I–K).

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