素修饰酶之间的交叉对话控制了特定站点的DNA放大
Sweta Mishra1, Capucine Van Rechem1, Sangita Pal1
1Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, 13(th) Street, Charlestown, MA 02129, USA.
Cell
|July 31, 2018
概括
染色体调节器控制瘤中的DNA复制数增加. 特定的H3K4甲基化通路和涉及KDM4B和KDM5B的独特网络调节特定位置的DNA放大.
科学领域:
- 表观遗传学
- 癌症生物学
- 基因组学
背景情况:
- 获得的染色体DNA放大是许多癌症的标志.
- 虽然KDM4A在暂时的特定站点副本数增长 (TSSG) 中的作用已知,但其他驱动这些增长的机制仍然不清楚.
研究的目的:
- 确定参与控制特定位点DNA复制的新型染色体调节剂.
- 阐明H3K4甲基化状态和相关调节器协调TSSG的机制.
主要方法:
- 研究了H3K4修饰色素调节剂与H3K9/H3K36调节剂的功能.
- 分析了KDM5A,COMPASS/KMT2甲基转移酶和MLL1-KDM4B-KDM5B网络在调节DNA拷贝数中的作用.
主要成果:
- 发现H3K4-修饰色素调节剂与H3K9/H3K36调节剂合作调节TSSG.
- 证明KDM5A和COMPASS/KMT2甲基转移酶通过H3K4甲基化和KDM4A招募影响TSSG位点.
- 确定了一个KDM4A独立的通路 (MLL1-KDM4B-KDM5B),在特定的位置调节拷贝数.
结论:
- 这些发现揭示了一个表观遗传地址系统,它控制了特定地点的DNA复制和放大.
- 这项研究强调了染色体修饰剂在驱动瘤相关的DNA拷贝数变化的复杂相互作用.
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