Developmental chromatin programs determine oncogenic competence in melanoma [ATAC-seq]
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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资源简介：
Oncogenes are only transforming in certain cellular contexts, a phenomenon called oncogenic competence. Here, using a combination of a human pluripotent stem cell-derived cancer model along with zebrafish transgenesis, we demonstrate that the transforming ability of BRAFV600E along with additional mutations depends upon the intrinsic transcriptional program present in the cell of origin. In both systems, melanocytes are largely resistant to mutations, whereas both neural crest and melanoblast populations are readily transformed. Profiling reveals that progenitors have higher expression of chromatin modifying enzymes such as ATAD2, a melanoma competence factor that forms a complex with SOX10 and allows for expression of downstream oncogenic and neural crest programs. These data suggest that oncogenic competence is mediated by regulation of developmental chromatin factors, which then allow for proper response to those oncogenes.
提供机构：
Memorial Sloan Kettering Cancer Center
创建时间：
2022-02-20
