21.09.2020

New research from the Nodine Group uncovers how chromatin affects siRNA expression

Chromatin in eukaryotic genomes is broadly divided into two classes: euchromatin, which are more open regions containing expressed genes, and heterochromatin, which is more densely packed and contains non-expressed regions including transposable elements (TEs), whose activation can be detrimental to genome integrity. In animals, fungi and plants, small interfering RNAs (siRNAs) promote heterochromatin formation and DNA methylation to silence TEs. However, little is known about how chromatin affects the expression of siRNAs. New research from the Nodine Group, led by PhD student Ranjith Papareddy, addressed how siRNA expression is influenced by chromatin. Using tools developed over the last several years at the GMI, the team was able to study siRNA expression and DNA methylation during Arabidopsis embryo development.

They found that expression of TE-derived siRNAs during development could be grouped into two classes based on whether the TEs were located in euchromatin or heterochromatin. siRNAs derived from euchromatic TEs gradually increased during embryogenesis, and their expression was maintained during later stages of vegetative development. Silencing of the corresponding TEs occurs by siRNA-dependent DNA methylation. In contrast, they observed a burst of siRNA expression from heterochromatic TEs just after fertilization, and expression rapidly decreased during embryo maturation. These heterochromatic siRNAs contributed to de novo methylation and formation of heterochromatin at their corresponding TEs, and DNA methylation and silencing was maintained independent of siRNAs after embryogenesis.

Zygotes require a burst of gene expression and protein production immediately after fertilization, and this coincides with chromatin decondensation. Therefore, zygotes run the risk of inadvertently activating and mobilizing TEs when heterochromatin is relaxed. Because all cell types, including the gametes, are derived from zygotes, decondensation of chromatin at this critical stage could be especially detrimental to genome integrity. Interestingly, hundreds of ribosomal RNAs (rRNAs) that fuel growth are co-localized with TEs in heterochromatin. These new results indicate that chromatin decondensation directly after fertilization enables the production of both rRNAs and TE-derived siRNAs, which either promote cell growth or heterochromatic TEs, respectively. As the heterochromatic TEs become silenced, the machinery to produce siRNAs from euchromatic TEs becomes more available. Euchromatic TEs are then silenced by mechanisms which require the continual presence of siRNAs. Together, the distinct expression patterns of siRNAs from the two classes of chromatin provide a system for the cell to recapitulate TE silencing despite the need to relax heterochromatin to enable rapid growth. Interestingly, similar changes in chromatin compaction have also been observed in response to heat stress, and expression of siRNAs from these regions during stress may allow the cell to reconstitute heterochromatin to prevent TE mobilization. Altogether, Papareddy et al. found that the interplay between chromatin and siRNAs enables a cell-autonomous mechanism to simultaneously enable maximal cell growth and maintain transposon methylome homeostasis throughout development including in the future germ line.

Papareddy RK, Páldi K, ..., Nodine MD (2020) Chromatin regulates expression of small RNAs to help maintain transposon methylome homeostasis in Arabidopsis. Genome Biol 21(1):251