PT  - JOURNAL ARTICLE
AU  - Aaron C. Daugherty
AU  - Robin Yeo
AU  - Jason D. Buenrostro
AU  - William J. Greenleaf
AU  - Anshul Kundaje
AU  - Anne Brunet
TI  - Chromatin accessibility dynamics reveal novel functional enhancers in <em>C. elegans</em>
AID  - 10.1101/088732
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 088732
4099  - http://biorxiv.org/content/early/2017/06/28/088732.short
4100  - http://biorxiv.org/content/early/2017/06/28/088732.full
AB  - Chromatin accessibility, a crucial component of genome regulation, has primarily been studied in homogeneous and simple systems, such as isolated cell populations or early-development models. Whether chromatin accessibility can be assessed in complex, dynamic systems in vivo with high sensitivity remains largely unexplored. In this study, we use ATAC-seq to identify chromatin accessibility changes in a whole animal, the model organism C. elegans, from embryogenesis to adulthood. 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. We find that over 5,000 distal non-coding regions exhibit dynamic changes in chromatin accessibility between developmental stages, and could thereby represent putative enhancers. When tested in vivo, several of these putative enhancers indeed drive novel cell-type-and temporal-specific patterns of expression. Finally, by integrating transcription factor binding motifs in a machine learning framework, we identify EOR-1 as a unique transcription factor that may regulate chromatin dynamics during development. 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.