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

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. To address this, we developed ChIP-DIP (ChIP Done In Parallel) 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 histone modifications, 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 stimulation. Next, we explored quantitative histone combinations 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 lab and experimental system. ChIP-DIP was used to simultaneously map DNA-associated proteins in human K562 cells, mouse embryonic stem cells and primary mouse dendritic cells.