Induction and maintenance of nonsymmetrical DNA methylation in Neurospora.
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')CpGGpC(5') or (5')CpNpGGpNpC(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 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.
Institute of Molecular Biology, University of Oregon, Eugene 97403-1229, USA. selker@molbio.uoregon.edu
Eric U
EU
Selker
Michael
M
Freitag
Gregory O
GO
Kothe
Brian S
BS
Margolin
Michael R
MR
Rountree
C David
CD
Allis
Hisashi
H
Tamaru
D019175:DNA Methylation; D004271:DNA, Fungal; D006655:Histone Deacetylases / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism; D009491:Neurospora / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D011496:Protein Methyltransferases
D004271:DNA, Fungal; D006657:Histones; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006655:Histone Deacetylases