qChIP-MS reveals the local chromatin composition by label-free quantitative proteomics

Chromatin immunoprecipitation (ChIP) has been a cornerstone for epigenetic analyses over the last decades, but even coupled to sequencing approaches (ChIP-seq), it is ultimately limited to one protein at a time. In a complementary effort, we here combine ChIP with label-free quantitative mass spectrometry (qChIP-MS) to interrogate local chromatin compositions. We demonstrate the versatility of our approach at telomeres, with transcription factors, in tissue and by dCas9-mediated locus-specific enrichment. Chromatin function depends on complex local protein environments. Here, the authors describe qChIP-MS, a simple, robust and quantitative method to map protein composition at defined chromatin regions and reveal local chromatin states.