Health,Stem Cells, and Technology

Thursday, March 31, 2016

A New Methylation Target - DNA methylation on N6-adenine in mammalian embryonic stem cells


A new means for environmental regulation of DNA in mammals has been discovered. A long held view by many scientist was that 5-methylcytosine is the only form of DNA methylation in mammalian genomes. In a new study published this week in Nature, Wu et al identify N6-methyladenine as another form of DNA modification in mouse embryonic stem cells.

The DNA of most organisms is composed of four standard bases and a small set of modified bases that are produced enzymatically from these four after DNA replication. One modified base, N6-methyladenine (N6mA), is prevalent in prokaryotes (bacteria and archaea), but whether it is found in mammals has remained unclear. In a paper online in Nature, Wu et al.report the existence of N6mA in mouse stem cells. This exciting discovery is enhanced by the identification of an enzyme that removes methyl groups from N6mA, and by the finding that the modification is enriched in certain regulatory DNA sequences — data that together provide clues to N6mA's possible function in mammalian genomes.

The new study suggests that N6-methyladenine has developed a new role in epigenetic silencing in mammalian evolution distinct from its role in gene activation in other organisms. The results demonstrate that N6-methyladenine constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes. This is another mechanism by which the environment can regulate DNA by modifying the chemical structure of DNA by adding CH3, a methyl group, to the base. This in turn can suppress expression of the targeted DNA sequence.

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