SUMO protease FUG1, histone reader AL3 and the PRC1 Complex are integral to repeat-expansion induced epigenetic silencing inArabidopsis thaliana

Abstract

Epigenetic gene silencing induced by expanded repeats can cause diverse phenotypes ranging from severe growth defects in plants to genetic diseases such as Friedreichs ataxia in humans (1). The molecular mechanisms underlying repeat expansion-induced epigenetic silencing remain largely unknown (2,3). Using a plant model, we have previously shown that expanded repeats can induce smallRNAs which in turn can lead to epigenetic silencing through the RNA-dependent DNA methylation pathway (4,5). Here, using a genetic suppressor screen, we confirm a key role for the RdDM pathway and identify novel components required for epigenetic silencing caused by expanded repeats. We show that FOURTH ULP LIKE GENE CLASS 1 (FUG1)- a SUMO protease, ALFIN-LIKE 3 - a histone reader and LIKE HETEROCHROMATIN 1 (LHP1) - a component of the PRC1 complex are required for repeat expansion-induced epigenetic silencing. Loss of any of these components suppress repeat expansion-associated phenotypes. SUMO protease FUG1 physically interacts with AL3 and perturbing its potential SUMOylation site disrupts its nuclear localisation. AL3 physically interacts with LHP1 of the PRC1 complex and the FUG1-AL3-LHP1 module is essential to confer repeat expansion-associated epigenetic silencing. Our findings highlight the importance post-translational modifiers and histone readers in epigenetic silencing caused by repeat expansions.

Involvement of Alfin-Like Transcription Factors in Plant Development and Stress Response

“…For example, the SUMO protease FUG1 physically interacts with AL3, and interference with its potential SUMOylation site disrupts its nuclear localization. AL3 interacts with LHP1 of the PRC1 complex, and the FUG1-AL3-LHP1 module is essential for conferring repeat amplification-associated epigenetic silencing of the SUMO protease FUG1, histone reader AL3, and PRC1 complex, which are integral to repeat expansion-induced epigenetic silencing in A. thaliana [42]. Similarly, cluster and conserved motif analyses revealed that the AL family proteins contained two conserved domains, the Alfin domain and the PHD domain (Figure 2B).…”