Induction and maintenance of nonsymmetrical DNA methylation in Neurospora

Abstract

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 CpG͞GpC 5 or 5 CpNpG͞GpNpC 5 ). 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 C⅐G to T⅐A 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.histone methylation ͉ chromatin ͉ RIP ͉ epigenetics ͉ DNA methyltransferase M ore than 25 years ago, Holliday and Pugh (1) and Riggs (2) pointed out that the symmetrical nature of methylated sites ( 5Ј CpG͞GpC 5Ј

Preferential de Novo Methylation of Cytosine Residues in Non-CpG Sequences by a Domains Rearranged DNA Methyltransferase from Tobacco Plants

“…In contrast, the methylation pattern at asymmetric cytosines is usually not maintained after DNA replication. For it to occur, an asymmetric de novo methyltransferase would be required, and no clear evidence had been presented for the existence of such enzymes until the recent reports describing Dnmt3a to methylate not only CpG but also asymmetric cytosines (31), and DIM-2 of Neurospora crassa to be responsible for cytosine methylation at symmetrical and asymmetrical sites (32). In plants, no enzyme has been assigned so far to catalyze cytosine methylation in asymmetric sites.…”

Neurospora crassa, a Model System for Epigenetics Research

“…2 in Li and Zhang 2014). Although results of a variety of in vitro and in vivo studies have supported the "maintenance methylase" model, mechanisms for maintenance methylation that do not rely on faithful copying at symmetrical sites can be imagined and may be operative in a variety of organisms (e.g., Selker 1990b; Selker et al 2002). The possibility that the observed methylation at asymmetric sites represented "de novo methylation" was exciting because mechanisms that blindly propagate methylation patterns can complicate the determination of which sequences are methylated in the first place.…”

Confining euchromatin/heterochromatin territory: jumonji crosses the line

“…2; . A methyl DNA-binding activity has been identified in N. crassa cell extracts (Selker et al 2002). Thus, it is reasonable to assume that, despite a limited feedback loop, factors that read DNA methylation are required to reinforce the establishment of H3K9me3 by DIM-5 HMT under certain conditions also in Neurospora.…”