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.

通过将数千种调节蛋白动态定位到精确的基因组区域来控制基因表达。了解这种细胞类型特异性过程一直是一个长期的目标，但仍然具有挑战性，因为 DNA-蛋白质图谱方法通常一次研究一种蛋白质。在这里，为了解决这个问题，我们开发了平行进行的染色质免疫沉淀 （ChIP-DIP），以在单个实验中生成数百种不同调节蛋白的全基因组图谱。ChIP-DIP 可在大型池（>160 蛋白）内为所有类型的 DNA 相关蛋白（包括修饰的组蛋白、染色质调节因子和转录因子）同时在多种条件下生成高精度图谱。首先，我们使用 ChIP-DIP 测量 LPS 刺激后原代树突状细胞的时间染色质动力学。接下来，我们探索了组蛋白修饰的定量组合，这些修饰定义了不同类别的调节元件，并表征了它们在人和小鼠细胞系中的功能活性。总体而言，ChIP-DIP 可在任何分子生物学实验室和实验系统中生成联盟规模的上下文特异性蛋白质定位图。