Induction and maintenance of nonsymmetrical DNA methylation in Neurospora
2002
Selker, E.U. | Freitag, M. | Kothe, G.O. | Margolin, B.S. | Rountree, M.R. | Allis, C.D. | Tamaru, H.
One can imagine a variety of mechanisms that should result in self-perpetuating biological states. It is generally assumed that cytosine methylation is propagated in eukaryotes by enzymes that specifically methylate hemimethylated symmetrical sites (e.g., 5'CpG/GpC5' or 5'CpNpG/GpNpC5'). Although there is wide support for this model, we and others have found examples of methylation that must be propagated by a different mechanism. Most methylated regions of the Neurospora genome that have been examined are products of repeat-induced point mutation, a premeiotic genome defense system that litters duplicated sequences with C.G to T.A mutations and typically leaves them methylated at remaining cytosines. In general, such relics of repeat-induced point mutation are capable of triggering methylation de novo. Nevertheless, some reflect a mechanism that can propagate heterogeneous methylation at nonsymmetrical sites. We propose that de novo and maintenance methylation are manifestations of a single mechanism in Neurospora, catalyzed by the DIM-2 DNA methyltransferase. The action of DIM-2 is controlled by the DIM-5 histone H3 Lys-9 methyltransferase, which in turn is influenced by other modifications of histone H3. DNA methylation indirectly recruits histone deacetylases, providing the framework of a self-reinforcing system that could result in propagation of DNA methylation and the associated silenced chromatin state.
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