Conservation and divergence of methylation patterning in plants and animals

Abstract

Cytosine DNA methylation is a heritable epigenetic mark present in many eukaryotic organisms. Although 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 organisms. Furthermore, genes appear to be the major target of methylation in Ciona and honey bee. 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, 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.BS-Seq | epigenetic profiling | DNA methylation | gene body methylation | UHRF1C ytosine DNA methylation is an epigenetic mark important in many gene regulatory systems, including genomic imprinting, X-chromosome inactivation, silencing of transposons and other repetitive DNA sequences, as well as expression of endogenous genes. Methylation is conserved in most major eukaryotic groups, including many plants, animals, and fungi, although it has been lost from certain model organisms such as the budding yeast Saccharomyces cerevisiae and nematode worm Caenorhabditis elegans (1-3). DNA methylation can be categorized into three types according to the sequence context of the cytosines, namely CG, CHG, and CHH (H = A, C, or T). CG methylation is maintained by conserved Dnmt1 DNA methyltransferase enzymes. CHH methylation, and, to some extent CHG methylation, is generally maintained by the activity of the conserved Dnmt3 methyltransferases, whereas high levels of CHG methylation seen in the model plant Arabidopsis are maintained by the plant-specific methyltransferase CMT3 (2, 3). Generally speaking, DNA methylation is thought to occur "globally" in vertebrates, with CG sites being heavily methylated genome-wide except for those in CpG islands, whereas invertebrates, plants, and fungi have "mosaic" methylation, characterized by interspersed methylated and unmethylated domains (4). These differences are an interesting starting point for studying divergence in methylation pathways and regulatory mechanisms; however, determining precise genomescale methylation patterns has been a challenge for complex genomes until the recent development of high-throughput sequencing technology. In this paper, we generated shotgun bisulfite sequencing data to profile DNA methylation in eight eukaryotic organisms. These organisms display wide variations in methylati...

Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes

“…Rather, because of the reduction in overall levels of active marks at promoters, we thought it was possible that lack of DNA methylation was causing a global decrease in transcription. We also note that DNA methylation is found in the body of genes and that studies have shown a correlation between gene body methylation and transcript levels [18][19][20] bodies is much lower in DKO1 cells ( Figure 4A), we found relatively similar transcriptome profiles in the two cell lines ( Figure 4B), suggesting that gene body methylation does not play a significant role in regulating gene expression in HCT116 and DKO1 cells. We did, however, identify three sets of transcripts that were affected by loss of DNA methylation (Additional file 8).…”

Gene silencing in microalgae: Mechanisms and biological roles

“…Methylation of the fifth carbon of cytosine is a widespread modification present in bacteria, archaea, and eukaryotes (Feng et al, 2010;Zemach et al, 2010;Huff and Zilberman, 2014). However, methylation of cytosine residues has not been detected in several model organisms such as Saccharomyces cerevisiae, Schizosaccharomyces pombe, and C. elegans (Capuano et al, 2014), suggesting that this modification is not essential for eukaryotic life.…”

“…The DNA of a vast array of organisms contains the modified base 5-methylcytosine, but genomes are methylated in different ways and with different consequences in diverse species (Feng et al, 2010;Zemach et al, 2010;Law and Jacobsen, 2010;Huff and Zilberman, 2014). Introduction of a methyl group at the C5 position of cytosine is catalyzed by a large family of DNA methyltransferases, including six subfamilies characterized by catalytic domains associated with N-terminal or C-terminal extensions containing distinct motifs (Goll and Bestor, 2005;Ponger and Li, 2005;Huff and Zilberman, 2014).…”

Genomic DNA methylation analyses reveal the distinct profiles in castor bean seeds with persistent endosperms

“…In addition, we noted that the expression levels of most genes were distinct between the early and late stages of endosperm and embryo development, implying that the genomic DNA methylation level within endosperm and embryo might be dynamic with seed development. To obtain the genomic DNA methylation profiles at single nucleotides, we examined the DNA methylation extent and pattern in endosperm and embryo tissues by high-throughput bisulfite-treated DNA sequencing techniques, which had been broadly applied in genomic DNA methylation studies (Feng et al, 2010;Zemach et al, 2010b). Our bisulfite sequencing yielded about 120 million paired-end reads, and 88% of reads were mapped into the castor bean genome with an effective depth of 313 coverage (Supplemental Table S1).…”

“…Methylated cytosine residue, also called the fifth nucleotide, is one of the most well-studied epigenetic marks found extensively in eukaryotes (Feng et al, 2010;Zemach et al, 2010b), in spite of the fact that the levels and patterns of cytosine DNA methylation appear to exhibit drastic changes among different eukaryotic organisms (Zhu, 2009;Zemach et al, 2010b). DNA methylation has shown broad-ranging functions, including the regulation of gene expression, involvement in chromatin organization, and protection of the genome from invading and mobile DNA elements (Heard and Disteche, 2006;Klose and Bird, 2006;Feinberg, 2007).…”