Single-cell multi-omic analysis reveals principles of transcription-chromatin interaction during embryogenesis

Establishing a cell-type-specific chromatin landscape is critical for the maintenance of cell identity during embryonic development. However, our knowledge of how this landscape is set during vertebrate embryogenesis has been limited, due to the lack of methods to jointly detect chromatin modifications and gene expression in the same cell. Here we present a multimodal measurement of full-length transcriptome and chromatin modifications in individual cells during early embryonic development in zebrafish. We show that before the formation of germ layers, the chromatin and transcription states of cells are uncoupled, and become progressively connected during gastrulation and somitogenesis. Silencing of key developmental genes is achieved by local spreading of repressive chromatin as development proceeds. We use a joint analysis of transcription factor (TF) expression and chromatin states to predict lineage-specific activators and repressors and identify a subset of TFs that are themselves epigenetically regulated. Altogether, our data resolves the dynamic relationship between chromatin and transcription during early embryonic development and clarifies how these two layers interact to establish cell identity.