美国哈佛医学院Pier Paolo Pandolfi、Jonathan D. Lee等研究人员合作开发新方法揭示白血病的表观基因组动态 。相关论文于2021年3月1日在线发表于国际学术期刊《自然—方法学》。

研究人员报道了一种双重转座酶-过氧化物酶方法，即整合的DNA和蛋白质标签（iDAPT），它可以检测与染色质可及区域相关的DNA（iDAPT-seq）和蛋白质（iDAPT-MS）。除了直接识别结合的转录因子外，iDAPT还可以推断其基因调控网络、蛋白质相互作用因子和染色质可及性的调控。研究人员应用iDAPT来分析了急性早幼粒细胞白血病中粒细胞分化的表观基因组学后果，从而产生了新的机制见解。

这些发现表明，iDAPT可作为研究动态表观基因组景观及其与生物学现象和疾病相关转录因子成分的平台。 

据悉，染色质的体系结构通过控制转录因子对基因调控位点的访问来调控真核细胞的状态。

附：英文原文

Title: Dual DNA and protein tagging of open chromatin unveils dynamics of epigenomic landscapes in leukemia

Author: Jonathan D. Lee, Joao A. Paulo, Ryan R. Posey, Vera Mugoni, Nikki R. Kong, Giulia Cheloni, Yu-Ru Lee, Frank J. Slack, Daniel G. Tenen, John G. Clohessy, Steven P. Gygi, Pier Paolo Pandolfi

Issue&Volume: 2021-03-01

Abstract: The architecture of chromatin regulates eukaryotic cell states by controlling transcription factor access to sites of gene regulation. Here we describe a dual transposase–peroxidase approach, integrative DNA and protein tagging (iDAPT), which detects both DNA (iDAPT-seq) and protein (iDAPT-MS) associated with accessible regions of chromatin. In addition to direct identification of bound transcription factors, iDAPT enables the inference of their gene regulatory networks, protein interactors and regulation of chromatin accessibility. We applied iDAPT to profile the epigenomic consequences of granulocytic differentiation of acute promyelocytic leukemia, yielding previously undescribed mechanistic insights. Our findings demonstrate the power of iDAPT as a platform for studying the dynamic epigenomic landscapes and their transcription factor components associated with biological phenomena and disease.

DOI: 10.1038/s41592-021-01077-8

Source: https://www.nature.com/articles/s41592-021-01077-8