近日，北京大学汤富酬等研究人员合作开发出一种单细胞长读CUT&Tag测序方法可用于在单个细胞中高效地进行染色质修饰分析。相关论文于2024年10月7日在线发表在《自然—方法学》杂志上。

研究人员开发了scNanoSeq-CUT&Tag，这是一种简化的方法，将经过修饰的目标位点切割和片段化（CUT&Tag）技术应用于纳米孔测序平台，实现单细胞层面的全基因组染色质修饰分析。

研究人员展示了scNanoSeq-CUT&Tag能够准确地在单细胞分辨率下分析组蛋白标记和转录因子占据模式，并区分不同的细胞类型。scNanoSeq-CUT&Tag能够高效绘制等位基因特异性染色质修饰图谱，并允许分析单个细胞内邻近区域的共占据模式。

此外，scNanoSeq-CUT&Tag能够准确检测人类和小鼠基因组中重复元件的单拷贝染色质修饰。总体而言，scNanoSeq-CUT&Tag是一种高效的单细胞工具，能够对组蛋白标记和转录因子占据模式进行全面分析，特别是对于以往研究较少的复杂基因组区域和黑名单基因组区域。

据悉，染色质修饰是决定基因组功能的基础表观遗传标记，但对重复序列和复杂基因组区域的修饰进行分析仍具有挑战性。

附：英文原文

Title: scNanoSeq-CUT&Tag: a single-cell long-read CUT&Tag sequencing method for efficient chromatin modification profiling within individual cells

Author: Li, Qingqing, Guo, Yuqing, Wu, Zixin, Xu, Xueqiang, Jiang, Zhenhuan, Qi, Shuyue, Liu, Zhenyu, Wen, Lu, Tang, Fuchou

Issue&Volume: 2024-10-07

Abstract: Chromatin modifications are fundamental epigenetic marks that determine genome functions, but it remains challenging to profile those of repetitive elements and complex genomic regions. Here, we develop scNanoSeq-CUT&Tag, a streamlined method, by adapting modified cleavage under targets and tagmentation (CUT&Tag) to the nanopore sequencing platform for genome-wide chromatin modification profiling within individual cells. We show that scNanoSeq-CUT&Tag can accurately profile histone marks and transcription factor occupancy patterns at single-cell resolution as well as distinguish different cell types. scNanoSeq-CUT&Tag efficiently maps the allele-specific chromatin modifications and allows analysis of their neighboring region co-occupancy patterns within individual cells. Moreover, scNanoSeq-CUT&Tag can accurately detect chromatin modifications for individual copies of repetitive elements in both human and mouse genomes. Overall, we prove that scNanoSeq-CUT&Tag is a valuable single-cell tool for efficiently profiling histone marks and transcription factor occupancies, especially for previously poorly studied complex genomic regions and blacklist genomic regions.

DOI: 10.1038/s41592-024-02453-w

Source: https://www.nature.com/articles/s41592-024-02453-w