Developmental enhancers revealed by extensive DNA methylome maps of zebrafish early embryos

Hyung Joo Lee, Rebecca F. Lowdon, Brett Maricque, Bo Zhang, Michael Stevens, Daofeng Li, Stephen L. Johnson and Ting Wang ()
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Hyung Joo Lee: Washington University School of Medicine
Rebecca F. Lowdon: Washington University School of Medicine
Brett Maricque: Washington University School of Medicine
Bo Zhang: Washington University School of Medicine
Michael Stevens: Washington University School of Medicine
Daofeng Li: Washington University School of Medicine
Stephen L. Johnson: Washington University School of Medicine
Ting Wang: Washington University School of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract DNA methylation undergoes dynamic changes during development and cell differentiation. Recent genome-wide studies discovered that tissue-specific differentially methylated regions (DMRs) often overlap tissue-specific distal cis-regulatory elements. However, developmental DNA methylation dynamics of the majority of the genomic CpGs outside gene promoters and CpG islands has not been extensively characterized. Here, we generate and compare comprehensive DNA methylome maps of zebrafish developing embryos. From these maps, we identify thousands of developmental stage-specific DMRs (dsDMRs) across zebrafish developmental stages. The dsDMRs contain evolutionarily conserved sequences, are associated with developmental genes and are marked with active enhancer histone posttranslational modifications. Their methylation pattern correlates much stronger than promoter methylation with expression of putative target genes. When tested in vivo using a transgenic zebrafish assay, 20 out of 20 selected candidate dsDMRs exhibit functional enhancer activities. Our data suggest that developmental enhancers are a major target of DNA methylation changes during embryogenesis.

Date: 2015
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DOI: 10.1038/ncomms7315

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