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Marc Bühler


Non-coding RNAs and chromatin

Over the last decade, there has been a convergence of two seemingly disparate fields of study: chromatin biology and RNA turnover. Data from a variety of organisms have shown that the assembly of silent chromatin coincides with the presence or absence of non-protein-coding RNAs (ncRNAs). These range from long ncRNAs that have been classically implicated in the regulation of dosage compensation and genomic imprinting to small ncRNAs involved in heterochromatin assembly via the RNA interference (RNAi) pathway. This raises the question of how common ncRNAs are used to control gene expression at the level of chromatin.

Our goal is to further our understanding of the role of ncRNAs in chromatin-dependent gene regulation. We are taking advantage of the power of yeast and address fundamental questions by employing in parallel genetic, biochemical, advanced live cell imaging, proteomic and genomic approaches. By doing so we will get a better understanding of mechanisms underlying various diseases. Thus, we are investigating in higher eukaryotes some of the insights gained from working with yeast. Currently, the lab focuses on three major projects:

RNAi-mediated heterochromatin assembly in fission yeast
A surprising link between heterochromatin and the RNAi pathway was discovered in fission yeast and plants. More recently, similar mechanisms have been described in other eukaryotes. Thus, RNAi-mediated chromatin modification leading to heterochromatic gene silencing seems to be a widespread phenomenon in eukaryotes.

Co-transcriptional gene silencing (CTGS)
Our previous work in fission yeast has demonstrated that silencing of genes inserted into heterochromatin and heterochromatic repeat elements might itself be mediated by RNAi as well as exosome-mediated co-transcriptional processing events, rather than by shutting off transcription. This novel mode of gene silencing is referred to as "Co-Transcriptional Gene Silencing" (CTGS) and its mechanistic details remain largely unknown.

Trinucleotide repeat expansion diseases (TREDs)
TREDs are caused by expanded tracts of repeated triplet sequences and can be loosely categorized into two classes. The first class, referred to as ?polyglutamine (polyQ) diseases?, is characterized by exonic (CAG)n repeat expansions encoding polyQ tracts. The second class has its repeats in non-coding sequences and is of particular interest to us as they can be associated with epigenetic changes. Importantly, there are several lines of evidence that RNA could be involved in the pathogenesis of TREDs.

Additional information
FMI report pages for Marc Bühler

Contact
Marc Bühler
Gabi Gruber
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