荷兰乌得勒支大学医学中心Jop Kind研究组和美国加州大学圣巴巴拉分校化学系Siddharth S. Dey研究组，宣布发明了单细胞内同步量化蛋白质-DNA相互作用和转录组的方法。 这一研究成果发表在2019年7月出版的国际学术期刊《Nature Biotechnology》上。

该课题组人员通过联合单细胞DNA腺嘌呤甲基转移酶鉴定与同细胞内信使RNA测序，开发了一种同步量化蛋白质与DNA相互作用的新技术scDam&T-seq。课题组研究人员应用scDam&T-seq揭示了单个细胞内染色体组与核纤层之间的联系，或染色质易访问性与基因表达的相互关系。此外，课题组研究人员提供了多梳家族蛋白（PcG），RING1B和相关转录组的单细胞全基因组相互作用数据。他们的研究结果表明，scDam&T-seq能够有效区分培养在不同条件下小鼠胚胎干细胞,以及其不同的染色质景观。该方法能够用于分析异质组织中蛋白质所介导的调节细胞类型特异性转录机制。

据介绍，蛋白质与DNA的相互作用对于基因表达的调节至关重要。但是如何定义，在细胞间异质性中蛋白质与DNA的结合影响基因表达，仍然具有挑战性。

附：英文原文

Title: Simultaneous quantification of protein–DNA contacts and transcriptomes in single cells

Author: Koos Rooijers, Corina M. Markodimitraki, Franka J. Rang, Sandra S. de Vries, Alex Chialastri, Kim L. de Luca, Dylan Mooijman, Siddharth S. Dey, Jop Kind

Issue&Volume: Volume 37 Issue 7, July 2019

Abstract: Protein–DNA interactions are critical to the regulation of gene expression, but it remains challenging to define how cell-to-cell heterogeneity in protein–DNA binding influences gene expression variability. Here we report a method for the simultaneous quantification of protein–DNA contacts by combining single-cell DNA adenine methyltransferase identification (DamID) with messenger RNA sequencing of the same cell (scDam&T-seq). We apply scDam&T-seq to reveal how genome–lamina contacts or chromatin accessibility correlate with gene expression in individual cells. Furthermore, we provide single-cell genome-wide interaction data on a polycomb-group protein, RING1B, and the associated transcriptome. Our results show that scDam&T-seq is sensitive enough to distinguish mouse embryonic stem cells cultured under different conditions and their different chromatin landscapes. Our method will enable the analysis of protein-mediated mechanisms that regulate cell-type-specific transcriptional programs in heterogeneous tissues.

DOI: 10.1038/s41587-019-0150-y

Source: https://www.nature.com/articles/s41587-019-0150-y