Dnmt1-Independent CG Methylation Contributes to Nucleosome Positioning in Diverse Eukaryotes

Abstract

SUMMARY Dnmt1 epigenetically propagates symmetrical CG methylation in many eukaryotes. Their genomes are typically depleted of CG dinucleotides, because of imperfect repair of deaminated methylcytosines. Here, we extensively surveyed diverse species lacking Dnmt1 and show that, surprisingly, symmetrical CG methylation is nonetheless frequently present, catalyzed by a novel DNA methyltransferase family, Dnmt5. Numerous Dnmt5-containing organisms that diverged over a billion years ago exhibit clustered methylation specifically in nucleosome linkers. Clustered methylation occurs at unprecedented densities and directly disfavors nucleosomes, contributing to nucleosome positioning between clusters. Dense methylation is enabled by a novel regime of genomic sequence evolution that enriches CG dinucleotides, driving the highest CG frequencies known. Species with linker methylation have small, transcriptionally active nuclei that approach the physical limits of chromatin compaction. These features constitute a previously unappreciated genome architecture, in which dense methylation influences nucleosome positions, likely facilitating nuclear processes under extreme spatial constraints.

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.…”

“…Interestingly, some of the examined microalgae lack clearly identifiable homologs of Dnmt1/MET1, CMT, and Dnmt3/DRM methyltransferases (Table 1), but it is not certain that they are devoid of DNA cytosine methylation. For instance, the Prasinophyte algae (Ostreococcus lucimarinus, Bathycoccus prasinos, and M. pusilla CCMP1545) contain highly diverged DNA methyltransferases of the Dnmt5 subfamily and exhibit genomic CG methylation (Huff and Zilberman, 2014). In land plants or mammals, DNA cytosine methylation is often associated with the transcriptional silencing of transposable elements, repetitive DNA sequences, and some protein-coding genes, and plays a critical role in genomic imprinting, X-chromosome inactivation, and chromosome stability (Feng et al, 2010;Law and Jacobsen, 2010).…”

“…In land plants or mammals, DNA cytosine methylation is often associated with the transcriptional silencing of transposable elements, repetitive DNA sequences, and some protein-coding genes, and plays a critical role in genomic imprinting, X-chromosome inactivation, and chromosome stability (Feng et al, 2010;Law and Jacobsen, 2010). Gene body methylation is also highly conserved even though its precise function(s) remains an open question (Feng et al, 2010;Zemach et al, 2010;Huff and Zilberman, 2014). In contrast to this wealth of information, the role(s) of DNA cytosine methylation in microalgae is still poorly understood.…”

“…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).…”

“…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). In land plants, DNA cytosine methylation can occur in three sequence contexts namely CG, CHG, and CHH (where H = A, T, or C) and three DNA methyltransferase subfamilies have been implicated in the establishment and/or maintenance of methylation at these sequences (Goll and Bestor, 2005;Law and Jacobsen, 2010).…”