RT Journal Article SR Electronic T1 Epigenetic maintenance of DNA methylation after evolutionary loss of the de novo methyltransferase JF bioRxiv FD Cold Spring Harbor Laboratory SP 149385 DO 10.1101/149385 A1 Sandra Catania A1 Phillip A. Dumesic A1 Caitlin Stoddard A1 Sophie Cooke A1 Jordan Burke A1 Christina A. Cuomo A1 Geeta J. Narlikar A1 Hiten D. Madhani YR 2017 UL http://biorxiv.org/content/early/2017/06/13/149385.abstract AB After the initial establishment of symmetric cytosine methylation patterns by de novo DNA methyltransferases (DNMTs), maintenance DNMTs mediate epigenetic memory by propagating the initial signal. We find that CG methylation in the yeast Cryptococcus neoformans is dependent on a purely epigenetic mechanism mediated by the single DNMT encoded by the genome, Dnmt5. Purified Dnmt5 is a maintenance methyltransferase that strictly requires a hemimethylated substrate, and methylation lost by removal of Dnmt5 in vivo is not restored by its mitotic or meiotic reintroduction. Phylogenetic analysis reveals that the ancestral species had a second methyltransferase, DnmtX, whose gene was lost between 50 and 150 Mya. Expression of extant DnmtXs in C. neoformans triggers de novo methylation. These data indicate that DNA methylation has been maintained epigenetically by the Dnmt5 system since the ancient loss of the DnmtX de novo enzyme, implying remarkably long-lived epigenetic memory.Single sentence summary Epigenetic information can be inherited over geological timescales