Effect of metformin on histone modifications in lung cancer cells

The DNA regions that were associated with the metformin altered expressions of H3K4me3 and/or H3K27me3 were investigated by ChIP-seq, and the regions significantly up- or down-regulated by metformin were identified in H1299 cells. Over 80% of H3K4me3 were discovered within promoter regions, but less than 10% of H3K27me3 were observed in this area. Metformin significantly downregulated H3K4me3 level at the promoter regions of 1113 genes, but upregulated levels in the promoter regions of 1492 genes. Gene enrichment analysis revealed that abundant cell cycle related genes such as PIK3C3, CCNB2, CDK1, CDK6, and E2F8 were upregulated, while certain cell cycle suppressor genes such as CDKN1A (p21) and DDIT4 were downregulated. No specific biological functional cluster was detected in the H3K27me3 up- or downregulated genes. Examination of H3K4me3 and H3K27me3 in H1299 cells treated with or without 5mM metformin.