Aim: Epigenetic marks are critical regulators of chromatin and gene activity. Their roles in normal physiology and disease states, including cancer development, still remain elusive. Herein, the epigenomic change of H3K9me3, as well as its potential impacts on gene activity and genome stability, was investigated in an in vitro breast cancer transformation model.
Methods: The global H3K9me3 level was studied with western blotting. The distribution of H3K9me3 on chromatin and gene expression was studied with ChIP-Seq and RNA-Seq, respectively.
Results: The global H3K9me3 level decreases during transformation and its distribution on chromatin is reprogrammed. By combining with TCGA data, we identified 67 candidate oncogenes, among which five genes are totally novel. Our analysis further links H3K9me3 with transposon activity, and suggests H3K9me3 reduction increases the cell's sensitivity to DNA damage reagents.
Conclusion: H3K9me3 reduction is possibly related with breast cancer transformation by regulating gene expression and chromatin stability during transformation.
Keywords: H3K9me3; breast cancer transformation; epigenomics; genome stability; transcription regulation.