GSE113923 RNA-dependent epigenetic silencing directs transcriptional down regulation caused by intronic repeat expansions

Contributors : Hannes Eimer ; Sridevi Sureshkumar ; Avilash S Yadav ; Calvin Kraupner-Taylor ; Champa Bandaranayake ; Andrei Seleznev ; Tamblyn Thomason ; Stephen Fletcher ; Stephanie F Gordon ; Bernard J Carroll ; Sureshkumar BalasubramanianSeries Type : Expression profiling by high throughput sequencingOrganism : Arabidopsis thalianaTranscriptional down regulation caused by intronic triplet repeat expansions underlies diseases such as Friedreich?s ataxia. This down regulation of gene expression is coupled with epigenetic changes but the underlying mechanisms are unknown. Here, we show that an intronic TTC/GAA triplet expansion within the IIL1 gene of Arabidopsis thaliana results in accumulation of 24-nt siRNAs and repressive histone marks at the IIL1 locus, which in turn causes its transcriptional down regulation and an associated phenotype. Knocking down DICER LIKE-3 (DCL3), which produces 24-nt siRNAs, suppressed transcriptional down regulation of IIL1 and the expansion-associated phenotype. Furthermore, knocking down additional components of the RNA-dependent DNA Methylation (RdDM) pathway, also suppressed both transcriptional down regulation of IIL1 and the repeat expansion associated phenotype. Thus our results show that triplet repeat expansions can lead to local siRNA biogenesis, which in turn down regulates transcription through an RdDM-dependent epigenetic modification.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Arabidopsis thaliana Source Type: research