title: Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates.
abstract: Two-thirds of gene promoters in mammals are associated with regions of non-methylated DNA, called CpG islands (CGIs), which counteract the repressive effects of DNA methylation on chromatin. In cold-blooded vertebrates, computational CGI predictions often reside away from gene promoters, suggesting a major divergence in gene promoter architecture across vertebrates. By experimentally identifying non-methylated DNA in the genomes of seven diverse vertebrates, we instead reveal that non-methylated islands (NMIs) of DNA are a central feature of vertebrate gene promoters. Furthermore, NMIs are present at orthologous genes across vast evolutionary distances, revealing a surprising level of conservation in this epigenetic feature. By profiling NMIs in different tissues and developmental stages we uncover a unifying set of features that are central to the function of NMIs in vertebrates. Together these findings demonstrate an ancient logic for NMI usage at gene promoters and reveal an unprecedented level of epigenetic conservation across vertebrate evolution. DOI:http://dx.doi.org/10.7554/eLife.00348.001.
authors: Department of Biochemistry , University of Oxford , Oxford , United Kingdom ; Weatherall Institute of Molecular Medicine, University of Oxford , Oxford , United Kingdom.
authors: Hannah K
authors: HK
authors: Long
authors: David
authors: D
authors: Sims
authors: Andreas
authors: A
authors: Heger
authors: Neil P
authors: NP
authors: Blackledge
authors: Claudia
authors: C
authors: Kutter
authors: Megan L
authors: ML
authors: Wright
authors: Frank
authors: F
authors: Grützner
authors: Duncan T
authors: DT
authors: Odom
authors: Roger
authors: R
authors: Patient
authors: Chris P
authors: CP
authors: Ponting
authors: Robert J
authors: RJ
authors: Klose
mesh_terms: D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002645:Chickens / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D017124:Conserved Sequence; D018899:CpG Islands; D019175:DNA Methylation; D030541:Databases, Genetic; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008116:Lizards / Q000235:genetics; D051379:Mice; D010987:Platypus / Q000235:genetics; D011401:Promoter Regions, Genetic; D013045:Species Specificity; D014981:Xenopus / Q000235:genetics; D015027:Zebrafish / Q000235:genetics
keywords: Chicken; Chromatin; CpG islands; DNA methylation; Epigenetics; Evolutionary conservation; Human; Mouse; Xenopus; Zebrafish