Epigenetic regulation of intragenic transposable elements impacts gene transcription in Arabidopsis thaliana

Abstract

Genomes of higher eukaryotes, including plants, contain numerous transposable elements (TEs), that are often silenced by epigenetic mechanisms, such as histone modifications and DNA methylation. Although TE silencing adversely affects expression of nearby genes, recent studies reveal the presence of intragenic TEs marked by repressive heterochromatic epigenetic marks within transcribed genes. However, even for the well-studied plant model Arabidopsis thaliana, the abundance of intragenic TEs, how they are epigenetically regulated, and their potential impacts on host gene expression, remain unexplored. In this study, we comprehensively analyzed genome-wide distribution and epigenetic regulation of intragenic TEs in A. thaliana. Our analysis revealed that about 3% of TEs are located within gene bodies, dominantly at intronic regions. Most of them are shorter and less methylated than intergenic TEs, but they are still targeted by RNA-directed DNA methylation-dependent and independent pathways. Surprisingly, the heterochromatic epigenetic marks at TEs are maintained within actively transcribed genes. Moreover, the heterochromatic state of intronic TEs is critical for proper transcription of associated genes. Our study provides the first insight into how intragenic TEs affect the transcriptional landscape of the A. thaliana genome, and suggests the importance of epigenetic mechanisms for regulation of TEs within transcriptional gene units.

Methylome analysis reveals an important role for epigenetic changes in the regulation of the Arabidopsis response to phosphate starvation

“…Plant genomes contain numerous TEs that are often silenced by epigenetic changes, such as histone modifications and DNA methylation. Although TEs can be a target of epigenetic silencing to prevent the expression of TE genes, the epigenetic regulation of TEs can also affect the expression of nearby genes, adding complexity to their transcriptional control (35,36). The association of DmCs and DMRs located in TEs that are inserted within gene features [generelated transposable elements (GR-TEs)] showed that, although there was a slight predominance of hypermethylation (57 hyperDMRs, 431 hyper-DmCs) over hypomethylation (31 hypo-DMRs, 369 hypo-DmCs), this tendency was consistent only for TEs located in DEGs (Fig.…”

How retrotransposons shape genome regulation

“…This model called the “rheostat hypothesis” was demonstrated in vitro but direct evidence for it is limited. More recently, methylation status of intronic TEs in Arabidopsis thaliana was correlated with lower transcription of genes with TE insertions [53]. …”

DNA Methylation within Transcribed Regions

“…One exception is the genome of Arabidopsis, which contains relatively few intronic TEs. A recent analysis estimated that only 0.7% of annotated genes in the Arabidopsis genome contain intronic TEs (Le et al, 2015). However, genome organization of Arabidopsis is exceptional; most plant species have a large number of TEs within introns.…”

“…That is the case for intronic TEs in both maize and A. lyrata. Even in the exceptionally compact genome Arabidopsis, long introns often contain non-CpG methylation, mainly associated with TE insertions there (Saze et al, 2013;Le et al, 2015;Fig. 1).…”

“…Although EDM2 and IBM2 preferentially localize to the intronic heterochromatin, it is currently unclear how the maintenance of repressive heterochromatic states within the actively transcribed region is achieved. More counterintuitively, maintenance of heterochromatin marks such as DNA methylation and H3K9me within introns can be important for proper expression of genes containing that, as loss of heterochromatic modifications in mutants such as decrease in DNA methylation1 and methyltransferase1 (met1) leads to a transcription defect of these genes (Le et al, 2015). For example, a reduction of DNA methylation of the repetitive element in the IBM1 gene in the met1 mutant results in a premature termination of the transcripts in the upstream of the repeat sequence (Rigal et al, 2012).…”