@article{b9260ca569d34ee9a35bf3c23c1910f2,
title = "Developmental enhancers revealed by extensive DNA methylome maps of zebrafish early embryos",
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.",
author = "Lee, {Hyung Joo} and Lowdon, {Rebecca F.} and Brett Maricque and Bo Zhang and Michael Stevens and Daofeng Li and Johnson, {Stephen L.} and Ting Wang",
note = "Funding Information: We thank Shannon Fisher for generously providing enhancer reporter plasmid and transposase expression plasmid. We thank Brian Stephens and Rachel Kerstetter for fish husbandry and technical assistance. We are grateful to everyone in Wang laboratory for helpful advice and discussions. H.J.L. is a McDonnell International Scholar (Washington University in St Louis) and a Kwanjeong Educational Foundation Abroad Scholar (South Korea). R.F.L. is supported by the NSF Graduate Research Fellowship Program DGE-1143954. B.Z. is supported by NIDA{\textquoteright}s R25 programme DA027995. S.L.J. is supported by R01GM05698. T.W. is supported by Basil O{\textquoteright}Connor Starter Scholar Research Award grant number 5-FY10-491 from the March of Dimes Foundation, American Cancer Society grant RSG-14-049-01-DMC and NIH grants R01HG007354, R01HG007175 and R01ES024992. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",
year = "2015",
month = feb,
day = "20",
doi = "10.1038/ncomms7315",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
}