Study : RNA-dependent epigenetic silencing directs transcriptional down regulation caused by intronic repeat expansions
Identification
Name
RNA-dependent epigenetic silencing directs transcriptional down regulation caused by intronic repeat expansions
Identifier
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Description
Transcriptional 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. Overall design: Comparison of the small RNA profile of 45 day old Arabidopsis thaliana accessions Col-0, Bur-0 and NS15 grown at 23°C or 27°C SD.
Genotype
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