Repeat sequences are present in plants to human to microbes, and unnatural repeat expansions are associated with several linked to several human genetic disorders. Expanded repeats carry peculiar features; repeats in either the noncoding/coding region often affect gene expression and protein function. However, the underlying mechanism of the repeat expansion-induced gene expression remains unclear. One of the problems is the lack of an appropriate model to study since most of the expansions are known primarily in human genetic diseases. Arabidopsis turns out to be the first non-human model that shows a trinucleotide repeat expansion-associated phenotypic variation. The Arabidopsis wild strain harbors a triplet repeat expansion associated with a growth defect associated with the downregulation of gene expression. Over the years, we have developed Arabidopsis as a natural method to uncover the molecular mechanisms associated with repeat expansion-induced downregulation of gene expression. Recently, we discovered that repeat expansion leads to accumulation of 24nt siRNAs, which via RNA-directed DNA methylation (RdDM) pathway induces epigenetic gene silencing at repeat expanded genetic locus harbouring the expansion. However, several questions remain unanswered, including how cellular variability contributes to gene regulation. To address this gap, we performed a genetic suppressor screens and identified several genetic suppressors, which confirm the role of RdDM pathway and reveal novel components that are essential for repeat expansion-induced epigenetic gene silencing. Here, I will describe the novel genes and pathways we have uncovered that regulate repeat expansion-associated gene regulation. Our findings provide important insights into the molecular mechanisms underlying the association between trinucleotide repeat expansion and pathogenesis in Arabidopsis. Overall, our study has significant implications for understanding the underlying mechanisms of repeat-induced gene regulation and the pathogenesis non only in the plants, would aid in understanding the human genetic disorders associated with trinucleotide repeat expansions.