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高通量Oligopaint屏幕识别可使用药物的3D基因组调节者
Daniel S Park1,2, Son C Nguyen1,2, Randi Isenhart1,2
1Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nature
|July 12, 2023
概括
研究人员使用新的成像管道确定了300多个影响基因组折叠的因素. 抑制GSK3A激酶增加了染色质循环,突出显示了它在核结构中的作用.
科学领域:
- 基因组学
- 分子生物学
- 细胞生物学
背景情况:
- 人类基因组是一个由复杂的染色体相互作用控制的3D染色体聚合物.
- 了解调节这些相互作用的蛋白质至关重要,但有限.
- 已经确定了几种基因组折叠和核架构的调节者.
研究的目的:
- 确定调节基因组折叠和染色质相互作用的新型蛋白质因素.
- 开发和使用自动成像管道来定量测量染色体相互作用.
- 选人类可用药物基因组的基因组组织调节剂.
主要方法:
- 使用优化的Oligopaints (HiDRO) 自动成像管道开发高通量DNA或RNA标签.
- 在数千个样本中量化测量单细胞中的染色体相互作用.
- 选可使用药物的人类基因组以确定影响基因组折叠的因素.
主要成果:
- 确定了300多个影响基因组折叠的因素.
- 验证了43个调节拓相关领域之间的相互作用的基因.
- 证明抑制GSK3A激酶可以以凝聚素依赖的方式在全基因组范围内增加长距离染色质循环.
结论:
- 在维护核架构方面,GSK3A信号发挥着重要作用.
- 通过HIDRO管道,可以有效地识别空间基因组组织的机制.
- 许多因素调节基因组折叠, 为了解核组织提供了新的目标.
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