美国加州理工学院Mitchell Guttman团队发现，ChIP-DIP映射揭示数百种蛋白质与DNA的结合并识别多种基因调控元件。2024年11月25日，《自然—遗传学》杂志在线发表了这项成果。

研究人员表示，基因表达通过成千上万种调控蛋白质在精确基因组区域的动态定位来调控。理解这一细胞类型特异性的过程一直是一个长期目标，但由于DNA–蛋白质映射方法通常一次研究一种蛋白质，这一目标仍然具有挑战性。

为了解决这一问题，研究人员开发了平行染色质免疫沉淀（ChIP-DIP），在单次实验中生成数百种不同调控蛋白质的全基因组地图。ChIP-DIP在大规模蛋白质池（>160种蛋白质）中生成高度准确的地图，适用于所有类别的DNA结合蛋白，包括修饰组蛋白、染色质调节因子和转录因子，并能够同时覆盖多种条件。

首先，研究人员使用ChIP-DIP测量了LPS刺激后原代树突状细胞中的时间性染色质动态。接下来，研究人员探索了定义不同类别调控元件的组蛋白修饰的定量组合，并表征了这些元件在人类和小鼠细胞系中的功能活性。总体而言，ChIP-DIP能够在任何分子生物学实验室和实验系统中生成特定背景的蛋白质定位图谱，并具有协作规模的潜力。

附：英文原文

Title: ChIP-DIP maps binding of hundreds of proteins to DNA simultaneously and identifies diverse gene regulatory elements

Author: Perez, Andrew A., Goronzy, Isabel N., Blanco, Mario R., Yeh, Benjamin T., Guo, Jimmy K., Lopes, Carolina S., Ettlin, Olivia, Burr, Alex, Guttman, Mitchell

Issue&Volume: 2024-11-25

Abstract: Gene expression is controlled by dynamic localization of thousands of regulatory proteins to precise genomic regions. Understanding this cell type-specific process has been a longstanding goal yet remains challenging because DNA–protein mapping methods generally study one protein at a time. Here, to address this, we developed chromatin immunoprecipitation done in parallel (ChIP-DIP) to generate genome-wide maps of hundreds of diverse regulatory proteins in a single experiment. ChIP-DIP produces highly accurate maps within large pools (>160 proteins) for all classes of DNA-associated proteins, including modified histones, chromatin regulators and transcription factors and across multiple conditions simultaneously. First, we used ChIP-DIP to measure temporal chromatin dynamics in primary dendritic cells following LPS stimulation. Next, we explored quantitative combinations of histone modifications that define distinct classes of regulatory elements and characterized their functional activity in human and mouse cell lines. Overall, ChIP-DIP generates context-specific protein localization maps at consortium scale within any molecular biology laboratory and experimental system.

DOI: 10.1038/s41588-024-02000-5

Source: https://www.nature.com/articles/s41588-024-02000-5