鼠标基因组的空间组织及其在反复发生的染色体转位中的作用
Yu Zhang1, Rachel Patton McCord, Yu-Jui Ho
1Howard Hughes Medical Institute, Children's Hospital Boston and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Cell
|February 21, 2012
概括
基因组3D组织显著影响染色体转位,特别是在DNA双链断裂 (DSB) 附近. 空间接近,而不仅仅是基因组位置,驱动癌症基因组学中的转位形成.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 三维 (3D) 基因组组织对于细胞功能至关重要.
- 染色体转位是许多癌症的标志,可以来自DNA双链断裂 (DSB).
- 了解基因组架构和转位形成之间的相互作用是癌症基因组学中的关键.
研究的目的:
- 研究3D基因组组织对染色体转位形成的贡献.
- 在高分辨率的鼠标亲B细胞基因组空间地图中绘制与DSB相关的转位.
- 阐明空间近距离在驱动转移中的作用.
主要方法:
- 创建了一个高分辨率的Hi-C空间组织图的G1被捕鼠亲B细胞基因组.
- 采用高通量全基因组转位测序来映射来自目标DSB的转位.
- 使用电离辐射直接评估空间近距离效应的规范化DSB.
主要成果:
- 鉴定出RAG内核酶分裂的抗原受体位点是目标DSBs的主导转位伙伴.
- 转位在单个染色体沿线和基于先前存在的空间邻近性的其他染色体内的cis显著丰富.
- 该研究表明,空间接近与转位丰富之间存在直接关系.
结论:
- 3D基因组组织在指导染色体转位方面发挥着关键作用.
- DNA双链断裂的空间接近是转位形成的主要决定因素,独立于基因组位置.
- 这项研究提供了使用综合基因组方法对癌症基因组改变的新视角.
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