用脱氨酶对转录因子的全基因组单细胞和单分子足迹
Runsheng He1,2, Wenyang Dong1,2,3, Zhi Wang1,2,3
1Changping Laboratory, Beijing 102206, China.
概括
一种名为FOODIE的新技术在全基因组范围内绘制转录因子结合部位的地图,分辨率为单基. 这种方法揭示了转录因子如何协调特定细胞类型和组织中的基因表达.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 转录因子 (TFs) 调节基因表达,控制组织特异性,时间和强度.
- 绘制全基因组TF结合部位的地图对于理解功能基因组学至关重要.
- 现有的方法缺乏TF结合分析的单分子,单细胞分辨率.
研究的目的:
- 开发一种高分辨率技术,用于绘制人类基因组上的TF结合位点.
- 为了实现TF结合和合作性的单分子和单细胞分析.
- 研究特定细胞类型和组织中基因模块的TF协调.
主要方法:
- 开发了使用除氨酶 (FOODIE) 的足迹,用于接近单基分辨率的TF结合位点检测.
- 在酶去胺后利用单分子测序来量化TF结合分数.
- 应用单细胞FOODIE来识别细胞类型特定的TF足迹在异质组织,如大脑.
主要成果:
- FOODIE准确地测量了邻近的TF之间的TF绑定分数和合作性 (正或负).
- 单细胞FOODIE在复杂组织中成功检测出细胞类型特定的TF足迹.
- 确定了共同的TF,协调促进剂和增强剂中的管家和组织特异性相关基因模块 (CGM).
结论:
- FOODIE是一种可扩展,具有成本效益的高分辨率TF绑定站点映射方法.
- 该技术为单细胞水平的TF介导基因调节提供了洞察力.
- 开放的FOODIE数据库将促进对细胞系,人体组织和临床样本的研究.
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