The Landscape Of Histone Methylation Of Breast Cancer Stem Cells

Breast cancer, with the highest morbidity of woman diseases, threatens women’s health in the world. Breast cancer stem cells are speculated to be an important reason leading to breast cancer metastasizes and relapses. Cancer stem cells are a small group of cancer cells with capability of self-renewal and initiating heterogeneous tumor. The development of cancer is associated with abnormal histone modification, including histone methylation. In this study, we will investigate the landscape of histone methylation of breast cancer stem cells (CSC).This thesis aims to study the different landscape of histone methylation between breast cancer stem cells and non-breast cancer stem cells (NCSC) by means of bioinformatics method, and explore the epigenetic regulation mechanism of breast cancer stem cells. This study mainly includes sorting breast cancer stem cells by FACS, and H3K4me2 and H3K27me3 specific chromatin immunoprecipitation followed by sequencing and data analysis.The analysis results suggested that there were significant differences in histone methylation landscapes between CSC and NCSC. What’s more, the enrichment pattern of H3K27me3 between CSC and NCSC was more different which indicated that H3K27me3 may play a more important role in stemness maintaining of CSC. Besides, differentially binding sites of H3K4me2 and H3K27me3 enriched in pathways participant in tumor proliferation, metastasis and stem cell self-rewnal, such as MAPK, Wnt and GnRH pathway, which indicated that histone methylation regulated CSC specificity by epigeneticly regulated genes expression enriched in cancer stem cell associated pathways. And compared differential binding sites of H3K4me2 and H3K27me3, the enriched pattern of these two histone methylation were differential and may play different roles in cancer stem cell.