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Updated: Jan 16, 2026

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使用DNA甲基化和纳米孔序列测序对单个染色质纤维进行长期读取的核素组映射

Gert-Jan Kuijntjes¹, Tineke L Lenstra², John van Noort³

¹Division of Gene Regulation, The Netherlands Cancer Institute, Oncode Institute, Amsterdam, the Netherlands; Biological and Soft Matter Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden University, Leiden, the Netherlands.

Biophysical journal

|October 3, 2025

概括

这项研究引入了一种新的方法,用于使用长读测序精确地绘制单分子核细胞组图. 这种技术在基因转录过程中揭示了详细的染色质组织和异质性,进步了我们对基因调节的理解.

科学领域:

分子生物学分子生物学
基因组学就是基因组学.
生物物理学的生物物理.

背景情况:

细胞核将DNA组织成染色体,调节基因的可访问性.
像MNase-seq这样的当前方法提供了人群平均核细胞体占用率.
单分子分辨率是必要的,以获得对染色质动态的机械洞察力.

研究的目的:

开发一种精确的单分子核细胞核素组映射技术.
在转录过程中调查染色质组织异质性.
为了深入分析局部染色体异常.

主要方法:

结合了DNA甲基化,长期读取的纳米孔测序和基于统计物理的核细胞核素映射算法.
在核细胞定位元上使用复制的染色质进行体外验证.
在不同的转录条件下在Saccharomyces cerevisiae中全基因组应用.

主要成果:

精确的单分子核细胞足迹在几十kbp的DNA位置.
在转录激活 GAL 位点时观察到核细胞分布的显著异质性.
确定了与转录活性相关的RDN1重复中的核细胞占用的长距离相关性.

结论:

开发的试验提供了精确的单分子核细胞组映射与长读序列.
这种方法揭示了染色质异质性和与转录相关的长距离相关性.
它为分析各种生物过程中的染色质动态提供了增强的能力.

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