RNA-mediated transcriptional gene silencing is a conserved process where small RNAs target transposons and other sequences for repression by establishing chromatin modifications. A central element of this process are long non-coding RNAs (lncRNA), which in Arabidopsis thaliana are produced by a specialized RNA polymerase known as Pol V. Here we show that non-coding transcription by Pol V is controlled by preexisting chromatin modifications located within the transcribed regions. Most Pol V transcripts are associated with AGO4 but are not sliced by AGO4. Pol V-dependent DNA methylation is established on both strands of DNA and is tightly restricted to Pol V-transcribed regions. This indicates that chromatin modifications are established in close proximity to Pol V. Finally, Pol V transcription is preferentially enriched on edges of silenced transposable elements, where Pol V transcribes into TEs. We propose that Pol V may play an important role in the determination of heterochromatin boundaries.DOI: http://dx.doi.org/10.7554/eLife.19092.001
Eukaryotic genomes are pervasively transcribed, yet most transcribed sequences lack conservation or known biological functions. InArabidopsis thaliana, RNA polymerase V (Pol V) produces noncoding transcripts, which base pair with small interfering RNA (siRNA) and allow specific establishment of RNA-directed DNA methylation (RdDM) on transposable elements. Here, we show that Pol V transcribes much more broadly than previously expected, including subsets of both heterochromatic and euchromatic regions. At already established RdDM targets, Pol V and siRNA work together to maintain silencing. In contrast, some euchromatic sequences do not give rise to siRNA but are covered by low levels of Pol V transcription, which is needed to establish RdDM de novo if a transposon is reactivated. We propose a model where Pol V surveils the genome to make it competent to silence newly activated or integrated transposons. This indicates that pervasive transcription of nonconserved sequences may serve an essential role in maintenance of genome integrity.
RNA-mediated transcriptional silencing, in plants known as RNA-directed DNA methylation (RdDM), is a conserved process where small interfering RNA (siRNA) and long non-coding RNA (lncRNA) help establish repressive chromatin modifications. This process represses transposons and affects the expression of protein-coding genes. We found that in Arabidopsis thaliana AGO4 binding sites are often located distant from genes differentially expressed in ago4. Using Hi-C to compare interactions between genotypes, we show that RdDM-targeted loci have the potential to engage in chromosomal interactions, but these interactions are inhibited in wild-type conditions. In mutants defective in RdDM, the frequency of chromosomal interactions at RdDM targets is increased. This includes increased frequency of interactions between Pol V methylated sites and distal genes that are repressed by RdDM. We propose a model, where RdDM prevents the formation of chromosomal interactions between genes and their distant regulatory elements.
While heredity is predominantly controlled by what deoxyribonucleic acid (DNA) sequences are passed from parents to their offspring, a small but growing number of traits have been shown to be regulated in part by the non‐genetic inheritance of information. Transgenerational epigenetic inheritance is defined as heritable information passed from parents to their offspring without changing the DNA sequence. Work of the past seven decades has transitioned what was previously viewed as rare phenomenology, into well‐established paradigms by which numerous traits can be modulated. For the most part, studies in model organisms have correlated transgenerational epigenetic inheritance phenotypes with changes in epigenetic modifications. The next steps for this field will entail transitioning from correlative studies to causal ones. Here, we delineate the major molecules that have been implicated in transgenerational epigenetic inheritance in both mammalian and non‐mammalian models, speculate on additional molecules that could be involved, and highlight some of the tools which might help transition this field from correlation to causation.
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