Single‐cell dynamics of chromatin activity during cell lineage differentiation in Caenorhabditis elegans embryos

Elucidating the chromatin dynamics that orchestrate embryogenesis is a fundamental question in developmental biology. Here, we exploit position effects on expression as an indicator of chromatin activity and infer the chromatin activity landscape in every lineaged cell during Caenorhabditis elegans early embryogenesis. Systems‐level analyses reveal that chromatin activity distinguishes cellular states and correlates with fate patterning in the early embryos. As cell lineage unfolds, chromatin activity diversifies in a lineage‐dependent manner, with switch‐like changes accompanying anterior–posterior fate asymmetry and characteristic landscapes being established in different cell lineages. Upon tissue differentiation, cellular chromatin from distinct lineages converges according to tissue types but retains stable memories of lineage history, contributing to intra‐tissue cell heterogeneity. However, the chromatin landscapes of cells organized in a left–right symmetric pattern are predetermined to be analogous in early progenitors so as to pre‐set equivalent states. Finally, genome‐wide analysis identifies many regions exhibiting concordant chromatin activity changes that mediate the co‐regulation of functionally related genes during differentiation. Collectively, our study reveals the developmental and genomic dynamics of chromatin activity at the single‐cell level. SYNOPSIS This study investigates the influence of local chromatin environment on reporter gene expression during Caenorhabditis elegans embryogenesis, based on single‐cell lineage tracing and live‐cell imaging. The chromatin activity landscape is inferred in lineage‐resolved single cells during C. elegans early embryogenesis. Chromatin activity diversifies in a lineage‐dependent manner, accompanying lineage fate commitment and anterior‐posterior fate asymmetry. Chromatin activity converges on tissue‐specific states but retains memories of lineage origins that contribute to cell heterogeneity within tissues. Predetermination of analogous chromatin activity occurs in early progenitor cells during left‐right symmetry establishment. Graphical Abstract This study investigates the influence of local chromatin environment on reporter gene expression during Caenorhabditis elegans embryogenesis, based on single‐cell lineage tracing and live‐cell imaging.