Investigation of histone 4 lysine 20 triple methylation (h4K20ME3) in breast cancer

Genetic and epigenetic changes play a role in the development of breast cancer, the most common malignant disease in women. Alterations in histone modification pathways, as in many cancers, are associated with the development and progression of breast cancer. In mammalian cells, H4 lysine 20 (H4K20) methylation occurs at 3 different levels: mono- (H4K20me1), di- (H4K20me2) and tri- (H4K20me3). Of these, H4K20me3 is enriched in heterochromatic regions of the genome, telomeres, imprinted regions, and repeat elements, and is involved in transcriptional silencing of these regions. H4K20me3 is catalyzed by the SUV420H2 methyl transferase whose expression level has been reported to be altered in many cancers. While some studies report that H4K20me3 mark decrease in different cancers whilst others demonstrated an increase. In this study, we aimed to investigate SUV420H2 expression and H4K20me3 amounts in breast cancer. Additionally, the effect of SUV420H2 gene silencing on the survival of breast cancer cells was investigated. SUV420H2 gene expression was determined semi-quantitatively at mRNA level; the amount of H4K20me3 was measured in extracted histone proteins by ELISA-like approach. We found higher SUV420H2 expression in tumor tissues than in adjacent normal tissues. There was a remarkable relationship between hormone receptor status and SUV420H2 expression. The amount of H4K20me3 was also significantly higher in tumor tissues. Patients with advanced disease tend to have higher levels of H4K20me3. Inhibition of SUV420H2 gene resulted in stimulation of cell proliferation. The data of this study reveals that SUV420H2 and H4K20me3 levels are altered in breast cancer and SUV420H2 is associated with cell proliferation. Key Words: Breast Cancer, Epigenetic, Histone Methylation, H4K20me3, SUV420H2 The present work was supported by the Istanbul University Scientific Research Projects Coordination Unit. Project No. TDK-2017-27336