Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans
- Aaron C. Daugherty1,5,
- Robin W. Yeo1,5,
- Jason D. Buenrostro1,6,
- William J. Greenleaf1,2,
- Anshul Kundaje1,3 and
- Anne Brunet1,4
- 1Department of Genetics, Stanford University, Stanford, California 94305, USA
- 2Department of Applied Physics, Stanford University, Stanford, California 94305, USA
- 3Department of Computer Science, Stanford University, Stanford, California 94305, USA
- 4Glenn Laboratories for the Biology of Aging, Stanford University, Stanford, California 94305, USA
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↵5 These authors contributed equally to this work.
Abstract
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 Caenorhabditis 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 5000 distal noncoding 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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.226233.117.
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Freely available online through the Genome Research Open Access option.
- Received June 13, 2017.
- Accepted September 13, 2017.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
