Rewriting the DNA (hydroxy) methylation textbook
17 Oct 2012
DNA methylation is an epigenetic modification whose function and distribution is currently an intense focus of research. Two new articles published in the journal Genome Biology are sure to excite, provoke – and perhaps even mystify – the epigenetics field with reports of DNA methylation in very surprising places. One article shatters the assumption that DNA methylation is absent in nematodes, while the other, astonishingly, finds methylation in a species with no characterized DNA methyltransferase – an enzyme thought to be essential for generating methylated DNA.
C. elegans, science’s most studied nematode, is a bona fide methylation-free zone – a curious exception to the widespread presence of DNA methylation across the tree of life. By extension, conventional thinking has held that DNA methylation is missing from all nematodes. Until now – because researchers studying the parasite Trichinella spiralis describe, for the first time, the presence of both DNA methylation and a DNA methyltransferase in a nematode.
Dr Fei Gao (BGI-Shenzhen, China), lead author of the study, explained: “We observed changes in DNA methylation during the transitions between T. spiralis’s three life cycle stages. Interestingly, we also found evidence to suggest that DNA methylation might be controlling parasitism-related genes. Our surprising discovery therefore may open a new avenue for developing therapeutics against T. spiralis infection, through targeting DNA methylation processes.”
Co-author Prof Mingyuan Liu (Jilin University, China) continued: “T. spiralis is one of the most widespread meat-borne parasites. It infects a broad range of animals and in humans causes trichinosis, a serious disease, so there are important implications to anything we can learn about its biology.”
DNA methylation in T. spiralis can readily be explained by the presence of the (previously unnoticed) DNA methyltransferase – an enzyme that intriguingly has no known counterpart in any other nematode. But trickier to explain is the new report from Princeton University, New Jersey, of DNA methylation in the ciliate Oxytricha trifallax, an organism that has no recognizable DNA methyltransferase.
Prof Laura Landweber, who led the study together with Dr John Bracht, believes that “the discovery of DNA methylation in a ciliate species fundamentally extends our knowledge of this modification to a new branch on the eukaryotic tree of life.”
The complicated two-genome set-up of ciliates, in which one genome is a heavily edited and remixed form of a second genome (both residing in the same cell), makes reproduction a very complicated process, involving DNA rearrangement and elimination. Prof Landweber and her colleagues were “excited to discover that DNA methylation targets sequences for destruction during genome rearrangement”. Their study also shows that hydroxymethylation, the so-called “6th base”, could be an essential part of this rearrangement process.
The apparent absence of a known DNA methyltransferase in its genome means that Oxytricha is the only species in which the origin of its DNA methylation is a total mystery. Prof Landweber and colleagues controversially propose that a novel mechanism may be responsible for DNA methylation in these ciliates, and that it may be an ancient methylation machinery.
Both the nematode and ciliate articles, part of a special issue on epigenomics, will challenge and reenergize our thinking on many questions relating to DNA methylation – How did it evolve? What functions can it perform? Which enzymes can generate it? Is there any part of the tree of life where it is truly absent?
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Notes to Editors
1. Article details
Differential DNA methylation in discrete developmental stages of the parasitic nematode Trichinella spiralis
Fei Gao, Xiaolei Liu, Xiuping Wu, Xuelin Wang, Desheng Gong, Hanlin Lu, Yudong Xia, Yanxia Song, Junwen Wang, Jing Du, Siyang Liu, Xu Han, Yizhi Tang, Huanming Yang, Qi Jin, Xiuqing Zhang and Mingyuan Liu
Genome Biology 2012, 13:R100 doi:10.1186/gb-2012-13-10-r100 (17 October 2012)
Cytosine methylation and hydroxymethylation mark DNA for elimination in Oxytricha trifallax
John R Bracht, David H Perlman and Laura F Landweber
Genome Biology 2012, 13:R99 doi:10.1186/gb-2012-13-10-r100 (17 October 2012)
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