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  • Transcriptional Silencers: ...
    Segert, Julian A.; Gisselbrecht, Stephen S.; Bulyk, Martha L.

    Trends in genetics, 06/2021, Letnik: 37, Številka: 6
    Journal Article

    Silencers are regulatory DNA elements that reduce transcription from their target promoters; they are the repressive counterparts of enhancers. Although discovered decades ago, and despite evidence of their importance in development and disease, silencers have been much less studied than enhancers. Recently, however, a series of papers have reported systematic studies of silencers in various model systems. Silencers are often bifunctional regulatory elements that can also act as enhancers, depending on cellular context, and are enriched for expression quantitative trait loci (eQTLs) and disease-associated variants. There is not yet evidence of a ‘silencer chromatin signature’, in the distribution of histone modifications or associated proteins, that is common to all silencers; instead, silencers may fall into various subclasses, acting by distinct (and possibly overlapping) mechanisms. Silencers are less well-studied than enhancers, but a recent spate of papers has begun to systematically explore these repressive regulatory elements.Silencers are important for precise control of gene expression and are enriched for disease-associated regulatory variants.Most newly discovered silencers are bifunctional regulatory elements that also act as enhancers in other contexts. The traditional distinction between enhancers and silencers may be an oversimplification.Silencers appear to act by a variety of mechanisms, and may fall into various functionally distinct subclasses. This complicates the search for a predictive chromatin signature that would enable the rapid identification of silencers from high-throughput data.Understanding silencer function will be key to predicting the regulatory impact of genomic variation.