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Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans

ABSTRACT: 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.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE89608 | GEO | 2017/07/30

SECONDARY ACCESSION(S): PRJNA352701

REPOSITORIES: GEO

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Project description:modENCODE_submission_3372 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP81(official name : OP81 genotype : unc-119(ed3) III; wgIs81 [unc-119(+) eor-1::TY1::EGFP::3xFLAG] outcross : 0 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The EOR-1::EGFP fusion protein is expressed in the correct eor-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the EOR-1 transcription factor. made_by : R. Waterston and S. Kim ); Developmental Stage: L3; Genotype: unc-119(ed3) III; wgIs81 [unc-119(+) eor-1::TY1::EGFP::3xFLAG]; Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage L3; Target gene eor-1; Strain OP81(official name : OP81 genotype : unc-119(ed3) III; wgIs81 [unc-119(+) eor-1::TY1::EGFP::3xFLAG] outcross : 0 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The EOR-1::EGFP fusion protein is expressed in the correct eor-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the EOR-1 transcription factor. made_by : R. Waterston and S. Kim ); temp (temperature) 20 degree celsius

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Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans

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