Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans

Chromatin accessibility, a crucial component of genome regulation, has mostly been studied in homogenous and simple systems, such as isolated cell populations or early development models. Whether it can sensitively be assessed in complex, dynamic systems in vivo remains largely unexplored. In this study, we identify chromatin accessibility changes in a whole organism from embryogenesis to adulthood, using C. elegans as a model. Chromatin accessibility changes between developmental stages are highly reproducible, recapitulate histone modification changes, and reveal key regulatory aspects of the epigenomic landscape throughout organismal development. Even when derived from the chromatin of a whole organism, dynamic regions of chromatin accessibility are capable of identifying novel cell-type- and temporal-specific enhancers, which we functionally validate in vivo. Furthermore, by integrating transcription factor binding motifs into a machine-learning framework, we identify EOR-1 as a potential early regulator of chromatin accessibility changes. Our study provides a unique resource for C. elegans, a system in which the prevalence and importance of enhancers remains poorly characterized, and demonstrates the power of using whole organism chromatin accessibility to identify novel regulatory regions in complex systems. Overall design: Three independent biological replicates for three key life stages: early embryo, larval stage 3 (L3), and young adults, were tightly temporally synchronized, and nuceli isolated before performing the standard ATAC-seq protocol. In addition, an input control, Tn5 transposition of gDNA purified from mixed stage worms was produced.