调节性DNA的单细胞映射:蛋白相互作用
Wei-Yu Chi1,2,3,4, Sang-Ho Yoon1,2,3, Levan Mekerishvili1,2,3,4
1Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
bioRxiv : the preprint server for biology
|January 13, 2025
概括
我们开发了D&D-seq,这是一种新的单细胞技术,用于绘制转录因子结合DNA的位置. 这种方法揭示了DNA:蛋白相互作用如何在衰老,疾病和癌症中发生变化.
科学领域:
- 表观遗传学和基因组学
- 分子生物学分子生物学
- 单细胞分析 单细胞分析
背景情况:
- 基因表达受到转录因子 (TF) 和表观遗传信号的调节.
- 这些网络中断与衰老,疾病和癌症有关.
- 现有的方法限制了单细胞中DNA:蛋白相互作用的分析,阻碍了对调节网络的理解.
研究的目的:
- 开发一种新的单细胞技术,用于绘制DNA:蛋白相互作用的地图.
- 克服现有方法的局限性,以分析单细胞中转录因子结合的情况.
- 为了使基因调节在健康和疾病环境中的多式分析.
主要方法:
- 开发了对接和除菌,随后进行了测序 (D&D-seq),这是一个单细胞免疫结合DNA:蛋白质映射技术.
- 结合抗体结合纳米体与细胞因子基编辑器,以描述TF结合.
- 将D&D-seq集成到单单细胞多组工作流程中.
主要成果:
- 在批量和单细胞中,D&D-seq精确地分析了转录因子结合 (CTCF,GATA),具有高特异性和高效率.
- 该技术显示了最小的目标外活动和与批量ChIP-seq.高一致性.
- 应用于人类初级细胞,D&D-seq确定了CTCF结合部位,预测了3D染色体结构,并揭示了IDH2突变细胞中CTCF结合的改变.
结论:
- D&D-seq是一种用于直接映射TF和染色体重塑剂与DNA结合的转化技术,用于初级人类样本中的DNA.
- 这一进步为研究健康和疾病中的染色质和转录调节开辟了新的途径.
- 能够更深入地了解在病理上下文中的监管网络干扰.
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