A Role for RNAi in the Selective Correction of DNA Methylation Defects

Abstract

DNA methylation is essential for silencing transposable elements and some genes in higher eukaryotes, which suggests that this modification must be tightly controlled. However, accidental changes in DNA methylation can be transmitted through mitosis (as in cancer) or meiosis, leading to epiallelic variation. We demonstrated the existence of an efficient mechanism that protects against transgenerational loss of DNA methylation in Arabidopsis. Remethylation is specific to the subset of heavily methylated repeats that are targeted by the RNA interference (RNAi) machinery. This process does not spread into flanking regions, is usually progressive over several generations, and faithfully restores wild-type methylation over target sequences in an RNAi-dependent manner. Our findings suggest an important role for RNAi in protecting genomes against long-term epigenetic defects.

Repeat elements and the Arabidopsis DNA methylation landscape

“…Moreover, plants seem more prone to the inheritance of DNA methylation defects than mammals (Richards, 2006;Whitelaw and Whitelaw, 2008). Collectively, these observations indicate that DNA methylation patterns tend to be propagated across generations in plants, rather than re-established anew at each generation like in mammals.Nonetheless, DNA methylation and silencing can be restored in an RNAi-dependent manner over a subset of repeat sequences following ddm1-induced hypomethylation (Johannes et al, 2009;Teixeira et al, 2009). Typically, restoration takes place over several generations , which is consistent with the frequent progressivity of TE inactivation in maize and transgene silencing in many plant species (Chandler and Stam, 2004;Slotkin and Martienssen, 2007).…”

“…As mentioned earlier, DNA methylation of repeat elements is mostly constant among Arabidopsis accessions (Vaughn et al, 2007;Zhai et al, 2008;Zhang et al, 2008), yet some highly methylated repeat elements seem to produce hardly any siRNAs (Kasschau et al, 2007;Lister et al, 2008;Teixeira et al, 2009). This raises the question of how such repeat elements maintain DNA methylation over evolutionary time.…”

“…Furthermore, CHH methylation is not completely abolished in drm1drm2cmt3 triple mutants (Cokus et al, 2008;Lister et al, 2008). This and other observations suggest that some CHH methylation is in fact laid down by MET1 or additional DNA MTases, presumably in an RNAi-independent manner ( In addition to the factors listed above, the ATPase SWI2/SNF2 chromatin remodeler DECREASE IN DNA METHYLATION 1 (DDM1) has an essential role in the maintenance of high DNA methylation levels over repeat elements (Vongs et al, 1993;Jeddeloh et al, 1999;Lippman et al, 2004;Teixeira et al, 2009). Although the mechanism of action of DDM1 remains mysterious, studies carried out on the mammalian homolog lymphoid-specific helicase (LSH) suggest that it may serve as a recruiting factor for DNA MTases and histone deacetylases at target loci (Myant and Stancheva, 2008).…”

Flyway evolution is too fast to be explained by the modern synthesis: proposals for an ‘extended’ evolutionary research agenda

“…In the cellular epigenetic scenario, the presence or absence of methyl, acetyl or phosphate groups to the DNA or histones can transiently or permanently modify gene expression by altering the local chromatin structure (Johannes et al 2008 Jacobsen 2009). These cellular epigenetic changes can be induced by environmental and/or genetic factors, and can remain relatively stable over several generations (Teixeira et al 2009;Reinders et al 2009). Phenotype can also be changed by mechanisms other than (epi)genome variation (Fig.…”

DNA methylation polymorphism and stability in Chinese indica hybrid rice

“…Variation of DNA methylation can affect plant phenotypes [1] and impact some important agricultural traits, such as resistance to rice bacterial blight (BB) [2,3], plant height [4] and yield [5]. Allelic variation in DNA methylation appears to be inheritable in subsequent generations [68], and inheritance of DNA methylation may be due to RNAi [9]. In Arabidopsis, large regions of contiguous methylation remain as stable DNA sequences across 30 generations [1].…”