Project description: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. In lower 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. Bio-CAP was used to identify non-methylated regions of the genome in seven diverse vertebrates (human, mouse, platypus, chicken, lizard, frog and zebrafish) across a number of tissues.
Project description: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. In lower 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.
Project description:Vertebrates have highly methylated genomes at CpG positions while most invertebrates have sparsely methylated genomes. Therefore, hypermethylation is considered a major innovation that shaped the genome and the regulatory roles of DNA methylation in vertebrates. However, here we report that the marine sponge Amphimedon queenslandica, belonging to one of the earliest branching animal lineages, has evolved a hypermethylated genome with remarkable similarities to that of a vertebrate. Despite major differences in genome size and architecture, independent acquisition of hypermethylation reveal common distribution patterns and repercussions for genome regulation between both lineages. Genome wide depletion of CpGs is counterbalanced by CpG enrichment at unmethylated promoters, mirroring CpG islands. Furthermore, a subset of CpG-bearing transcription factor motifs are enriched at Amphimedon unmethylated promoters. We find that the animal-specific transcription factor NRF has conserved methyl-sensitivity over 700 million years, indicating an ancient cross-talk between transcription factors and DNA methylation. Finally, the sponge shows vertebrate-like levels of 5-hydroxymethylcytosine, the oxidative derivative of cytosine methylation involved in active demethylation. Hydroxymethylation is concentrated in regions that are enriched for transcription factor motifs and show developmentally dynamic demethylation. Together, these findings push back the links between DNA methylation and its regulatory roles to the early steps of animal evolution. Thus, the Amphimedon methylome challenges the prior hypotheses about the origins of vertebrate genome hypermethylation and its implications for regulatory complexity.
2019-08-02 | GSE124016 | GEO
Project description:A unified genealogy of modern and ancient genomes
| PRJEB46983 | ENA
Project description:Ancient high-coverage shotgun human genomes
Project description:Gene order, or microsynteny, is generally thought not to be conserved across metazoan phyla. Only a handful of exceptions, typically of tandemly duplicated genes such as Hox genes, have been discovered. Here, we performed a systematic survey for microsynteny conservation in 17 genomes and identified nearly 600 pairs of unrelated genes that have remained together across over 600 million years of evolution. Using multiple genome-wide resources, including several genomic features, epigenetic marks, sequence conservation and microarray expression data, we provide extensive evidence that many of these ancient microsyntenic arrangements have been conserved in order to preserve either (i) the coordinated transcription of neighboring genes, or (ii) Genomic Regulatory Blocks (GRBs), in which transcriptional enhancers controlling key developmental genes are contained within nearby “bystander” genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos to further investigate putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results show that ancient genomic associations are far more common in modern metazoans than previously thought – likely involving over 12% of the ancestral bilaterian genome – and that cis-regulatory constraints have played a major role in conserving the architecture of metazoan genomes. ChIP-seq H3K27me3 of 24hpf zebrafish embryos
Project description:Cytosine DNA methylation is a heritable epigenetic mark present in many eukaryotic organisms. While DNA methylation likely has a conserved role in gene silencing, the levels and patterns of DNA methylation appear to vary drastically among different organisms. Here, we used shotgun genomic bisulfite sequencing (BS-Seq) to compare DNA methylation in eight diverse plant and animal genomes. We found that patterns of methylation are very similar in flowering plants with methylated cytosines detected in all sequence contexts, whereas CG methylation predominates in animals. Vertebrates have methylation throughout the genome except for CpG islands. Gene body methylation is conserved with clear preference for exons in most of the organisms. Furthermore, genes appear to be the major target of methylation in Ciona and honeybee. Among the eight organisms, the green alga Chlamydomonas has the most unusual pattern of methylation, having non-CG methylation enriched in exons of genes rather than in repeats and transposons. In addition, we demonstrate that the Dnmt1 cofactor Uhrf1 has a conserved function in maintaining CG methylation in both transposons and gene bodies in the mouse, Arabidopsis, and zebrafish genomes. Comparison of methylation across eight eukaryotic organisms