功能增强器连接体和人类质瘤风险变体的系统解码
Jinfang Bi1, Weipeng Mo1, Man Liu2
1Department of Laboratory Medicine and Institute of Precise Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
研究人员确定了关键的遗传元素,称为增强剂,驱动着质瘤的生长. 他们发现,这些增强剂中的特定遗传变异通过改变基因表达来促进瘤的进展,为脑瘤提供了新的治疗标.
科学领域:
- 基因组学和分子生物学
- 癌症研究 癌症研究
- 神经瘤学神经瘤学
背景情况:
- 遗传和表观遗传变异与质瘤的进展有关.
- 在非编码区域中增强剂相关的遗传变异的机制尚不清楚.
- 识别驱动瘤生长的调节因素对于理解质瘤的发病过程至关重要.
研究的目的:
- 通过高通量查,在质瘤细胞中识别出促瘤增强剂.
- 阐明增强器连接体在质瘤进展中的作用.
- 研究质瘤风险相关的单核酸多形态 (SNP) 如何影响瘤发育.
主要方法:
- 高通量CRISPR干扰 (CRISPRi) 查以识别前瘤增强剂.
- 整合全基因组H3K27ac HiChIP数据以绘制增强剂-点基因相互作用.
- 通过CRISPR-Cas9介导的增强剂干扰和SNP编辑用于功能验证.
主要成果:
- 在质瘤中识别出促瘤增强剂及其向基因.
- 证明增强器连接体在促进质瘤进展中的重要作用.
- 验证了增强剂中的风险SNP可以通过增强剂连接组驱动质瘤的进展.
- 具体发现:一种具有风险SNP rs2297440的质瘤特异性增强剂通过招募MEIS1来调节SOX18表达,促进质瘤.
结论:
- 增强器连接体在质瘤进展中起着至关重要的作用.
- 增强剂中的遗传变异,特别是携带风险SNP的增强剂,有助于质瘤易感性.
- 该研究提供了关于质瘤分子机制的见解,并确定了潜在的治疗点.
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