Silencing: new faces of Morpheus' molecule.

Eukaryotic genomes contain large numbers of transposable elements that not only pose a threat to genome integrity but also regulate expression of certain proteincoding genes. The molecular mechanisms of transposon silencing are still not very well understood. Two papers in this issue of The EMBO Journal shed new light on the function of Morpheus’ molecule (MOM1), one of the most mysterious components of the silencing systems in plants. Transcriptional gene silencing is a process that controls expression of transposons and repetitive DNA elements. It is involved not only in maintaining genome integrity but also in regulating expression of genes that harbor transposons in their promoters. The core mechanism of transcriptional gene silencing involves establishment of DNA methylation and/or certain covalent modifications of histone tails, which block transcription by RNA Polymerases I, II or III. One of the most mysterious components of transcriptional gene silencing system in Arabidopsis thaliana is MOM1, named after the Greek god of dreams (Amedeo et al, 2000). It is distinct from most known components of transcriptional silencing pathways in plants, in that it silences transcription, but is not required to maintain DNA methylation associated with the silent state (Amedeo et al, 2000; Habu et al, 2006; Vaillant et al, 2006). Although based on sequence similarities MOM1 seemed to be a chromatin remodeling factor (Amedeo et al, 2000), the recent discovery that 87% of its sequence, including the SNF2 domain, is dispensable for silencing showed how little we know about the molecular mechanism of MOM1 function (Caikovski et al, 2008). Two papers in this issue of The EMBO Journal (Numa et al, 2009; Yokthongwattana et al, 2009) address the question of how MOM1 works. Yokthongwattana et al started with a clever forward genetic screen designed to find mutants in genes encoding proteins that are functionally related to MOM1. They identified a mutant in NRPE1, the largest subunit of RNA Polymerase V (Pol V), a specialized plant-specific RNA Polymerase. The mom1 nrpe1 double mutant displayed a dramatic loss of transcriptional gene silencing compared with the subtler effects of single mom1 or nrpe1 mutants. This suggested that both MOM1 and Pol V contribute to transcriptional silencing but that they work in parallel, non-redundant pathways. Pol V is known to function in an RNA-dependent DNA methylation (RdDM) pathway, where short interfering RNAs guide DNA methylation and transcriptional silencing to transposons and other repetitive DNA elements (Wierzbicki et al, 2008, 2009; Matzke et al, 2009). Thus, Yokthongwattana et al extended their genetic analysis to other components of the RdDM pathway and concluded that, at least for a subset of loci, MOM1 functions in a pathway parallel to RdDM. To determine whether this functional interaction between MOM1 and RdDM is of general importance, Yokthongwattana et al carried out an extensive transcriptome analysis. Genetic interactions between MOM1 and Pol V turned out to be quite complex and locus-specific (Figure 1). At some loci, double mutants showed disruption of silencing that was considerably stronger than in either individual mutant, thus confirming that MOM1 and Pol V can work in parallel. Surprisingly, at a different subset of loci the effects of mom1, nrpe1 and mom1 nrpe1 were very similar, suggesting that in these cases MOM1 and Pol V work in the same silencing pathway. At yet a third subset of loci, the silencing defects observed in nrpe1 were reversed in nrpe1 mom1 double mutants, suggesting that