结构变异导致癌症中的上下文依赖性瘤基因激活
Zhichao Xu1, Dong-Sung Lee2, Sahaana Chandran1
1Gene Expression Laboratory; Salk Institute for Biological Studies, La Jolla, CA, USA.
Nature
|December 8, 2022
概括
改变3D基因组组织的结构变异在癌症中很常见. 活动依接触模型可以预测特定的SVs的瘤基因激活,揭示不同的基因调节模式.
科学领域:
- 基因组学
- 癌症生物学
- 表观遗传学
背景情况:
- 高阶染色体结构通过远端元素调节基因表达.
- 改变3D基因组组织的结构变异 (SV) 可以导致疾病,特别是癌症.
- 为什么只有某些SV会影响基因表达的原因尚不清楚.
研究的目的:
- 识别癌症中反复发生的3D基因组结构变化.
- 确定特定的SVs对瘤基因激活的影响.
- 开发对SV对基因表达的影响的预测模型.
主要方法:
- 分析92个癌细胞系和患者样本的Hi-C数据.
- 通过CRISPR-Cas9基因组工程,
- 应用"接触式活动"模型.
主要成果:
- 在瘤基因 (MYC,TERT,CCND1) 中发现了反复发生的3D基因组结构改变.
- 通过"接触式活动"模型预测癌基因活性.
- 发现这些模型只能预测基因的子集,表明不同的调节机制.
结论:
- 影响3D基因组组织的SV在癌症中普遍存在.
- 对 SVs 对瘤基因激活的影响的预测规则正在出现.
- 不同的基因类利用涉及远端元素的不同调节模式.
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