Myc-mediated SDHA Acetylation Triggers Epigenetic Regulation of Gene Expression and Tumorigenesis

Trimethylated H3K4 (H3K4me3), which is often found surrounding the transcriptional start site of active genes, is strongly enriched in the promoter regions of Myc-targeted genes. Succinate, which inhibits JmjC domain-containing histone demethylases (JHDMs), can induce H3K4me3 level of the promoter regions. It's interesting to ask whether Myc can mediate H3K4me3 by inhibiting SDH activity and inducing cellular succinate level. Here, We used ChIP-seq to study Myc modulates H3K4me3 by altering succinate levels, dimethyl succinate (DMS), a membrane-permeable succinate analog, was introduced to treat P493-6 cells with high or depleted Myc expression. And we performed RNA-seq assays in Myc expressed or depleted P493-6 cells with or without DMS treatment. Besides, we also performed RNA-seq assays in Myc expressed or depleted P493-6 cells with or without 3-nitropropionic acid (3-NPA, SDH enzyme inhibitor) treatment. Overall design: P493-6 cells were treated with tetracycline (tet) or without for 48h in presence of methyl succinate (DMS) and followed by H3K4me3 ChIP-seq to address whether succinate can induce H3K4me3 level of the promoter regions in P493-6 cells with depleted Myc expression. Meanwhile, we also performed RNA extraction and sequenced on Illumina novaseq (Homo sapiens). Moreover, we also treated P493-6 cell with tet or without for 48h in presence of 3-nitropropionic acid (3-NPA, SDH enzyme inhibitor), followed by extracting RNA and sequenced on Illumina novaseq (Homo sapiens).