T-ChIC: multi-omic detection of histone modifications and full-length transcriptomes in the same single cell

Abstract Epigenetic mechanisms, such as histone modifications, are key regulators of transcription and maintenance of cell identity. While our knowledge concerning cell type-specific histone modifications has constantly increased, we still know little about the interplay between epigenetics and transcription at the level of the individual cell. To gain an understanding of this process, we developed T-ChIC (Transcriptome + Chromatin ImmunoCleavage), a method allowing for the detection of full-length transcripts and histone modifications in the same single cell. We applied this technique to an in vitro model of gastrulation and monitored the coordinated dynamics of the transcriptome and active and repressive histone modifications as mouse embryonic stem cells differentiate into the three germ layers. Our analysis reveals a germ layer-dependent coupling between chromatin regulation and transcriptional states.