PAX3-FOXO1 coordinates enhancer architecture, eRNA transcription, and controls RNA polymerase pause release at select gene targets [ATAC-Seq]. PAX3-FOXO1 coordinates enhancer architecture, eRNA transcription, and controls RNA polymerase pause release at select gene targets [ATAC-Seq]

This study aim to in-depth understand the function of a transcription factor fusion protein that drives the development of a highly aggressive pediatric malignancy. After engineered the endogenous PAX3-FOXO1 locus, we use chemical genetics to rapidly degrade the protein. This comprehensive, detailed, and accurate study with deep genomic analyses and deep proteomics provide a detailed mechanism by which PAX3-FOXO1 maintains an oncogenic transcriptional regulatory network. Overall design: Deep mechanistic analysis including proteomics and 15 parameter genomics.

本研究旨在深入解析驱动高侵袭性儿童恶性肿瘤发生的转录因子融合蛋白（transcription factor fusion protein）的功能。在对其内源性PAX3-FOXO1基因座完成工程化改造后，我们利用化学遗传学方法实现了该蛋白的快速降解。本研究通过深度基因组学与深度蛋白质组学分析，开展全面、细致且精准的研究，阐明了PAX3-FOXO1维持致癌性转录调控网络的具体分子机制。实验整体设计：涵盖蛋白质组学与15参数基因组学的深度机制分析。