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Elife February 26, 2013; 2 e00348.

Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates.

Long HK , Sims D , Heger A , Blackledge NP , Kutter C , Wright ML , Grützner F , Odom DT , Patient R , Ponting CP , Klose RJ .

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:

PubMed ID: 23467541
PMC ID: PMC3583005
Article link: Elife
Grant support: A15603 Cancer Research UK, MC_U137981013 Medical Research Council , 15603 Cancer Research UK, 202218 European Research Council, MC_UU_12009/8 Medical Research Council , MC_U137761446 Medical Research Council , WT0834922 Wellcome Trust , G1000902 Medical Research Council , 090018/Z/09/Z Wellcome Trust , CRUK_15603 Cancer Research UK, MRC_MC_U137981013 Medical Research Council , CRUK_A15603 Cancer Research UK, MRC_MC_U137761446 Medical Research Council , MRC_MC_UU_12009/8 Medical Research Council , ERC_202218 European Research Council

Genes referenced: act3 aptx dnaja1 ezh2 gnao1 gsx1 nkx2-2 nmi rnf2 smu1 sp9 suz12

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