Abstract
Upon sensing developmental or environmental cues, epigenetic regulators transform the chromatin landscape of a network of genes to modulate their expression and dictate adequate cellular and organismal responses. Knowledge of the specific biological processes and genomic loci controlled by each epigenetic regulator will greatly advance our understanding of epigenetic regulation in plants. To facilitate hypothesis generation and testing in this domain, we present EpiNet, an extensive gene regulatory network (GRN) featuring epigenetic regulators. EpiNet was enabled by (i) curated knowledge of epigenetic regulators involved in DNA methylation, histone modification, chromatin remodeling, and siRNA pathways; and (ii) a machine-learning network inference approach powered by a wealth of public transcriptome datasets. We applied GENIE3, a machine-learning network inference approach, to mine public Arabidopsis transcriptomes and construct tissue-specific GRNs with both epigenetic regulators and transcription factors as predictors. The resultant GRNs, named EpiNet, can now be intersected with individual transcriptomic studies on biological processes of interest to identify the most influential epigenetic regulators, as well as predicted gene targets of the epigenetic regulators. We demonstrate the validity of this approach using case studies of shoot and root apical meristem development.
Highlights
In eukaryotes, gene regulation occurs in the context of chromatin and nucleosomes, which is influenced by epigenetic modifications that pack genomic DNA and poise genes for activation or repression [1]
SDG8, a H3K36 methyltransferase, was shown to target hundreds of genes involved in defense, carbon metabolism, and reproductive development to modify their associated histones and gene expression levels [9], and it is required for proper responses to various environmental [10,11,12] and developmental signals [13]
Using meristematic development as a case study, we identified key epigenetic regulators that control a network of genes important for developmental processes in meristematic tissues of the shoot apical meristem (SAM) and root apical meristem (RAM), separately
Summary
Gene regulation occurs in the context of chromatin and nucleosomes, which is influenced by epigenetic modifications that pack genomic DNA and poise genes for activation or repression [1]. Epigenetic regulators can transform the chromatin landscape of a corresponding suite of genes to modulate their expression and dictate adequate cellular and organismal responses to developmental signals or environmental cues. Experimental evidence accumulated in the past 20 years established that epigenetic regulators and chromatin modifications play essential roles in modulating gene expression in response to developmental and environmental signals [3,4,5,6,7,8]. SDG8, a H3K36 (lysine 36 of histone subunit 3) methyltransferase, was shown to target hundreds of genes involved in defense, carbon metabolism, and reproductive development to modify their associated histones and gene expression levels [9], and it is required for proper responses to various environmental [10,11,12] and developmental signals [13]. A knowledge base to link each epigenetic regulator with specific biological processes and genome-wide targets is needed to move toward a genome-wide, systems-level understanding of epigenetic regulation
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