%0 Journal Article
%T Enhancers and silencers: an integrated and simple model for their function
%A Petros Kolovos
%A Tobias A Knoch
%A Frank G Grosveld
%A Peter R Cook
%A Argyris Papantonis
%J Epigenetics & Chromatin
%D 2012
%I BioMed Central
%R 10.1186/1756-8935-5-1
%X The complex linear organisation [1] of many metazoan genomes encodes regulatory sequences that can be categorised into two major groups: enhancers and silencers. Enhancers are short motifs that contain binding sites for transcription factors; they activate their target genes without regard to orientation and often over great separations in cis or in trans [2]. Silencers suppress gene expression [3] and/or confine it within specific chromatin boundaries (and thus are also called 'insulators') [4]. The interplay between these contrasting regulatory elements, their target promoters and epigenetic modifications at all levels of three-dimensional organisation (that is, nucleosomes, chromatin fibres, loops, rosettes, chromosomes and chromosome location) [5-9] fine-tune expression during development and differentiation. However, the mechanisms involved in this interplay remain elusive, although some can be computationally predicted [10]. Although enhancers and silencers have apparently opposite effects, accumulating evidence suggests they share more properties than intuition would suggest [11]. Herein we try to reconcile their apparently disparate modes of action. We suggest they act by tethering their target promoters close to, or distant from, hot spots of nucleoplasmic transcription (known as 'transcription factories') as they produce noncoding transcripts (ncRNAs) [12-15].Enhancers were characterised almost 30 years ago [16], but their functional definitions vary because of their flexibility of action (whether in cis or in trans) [17,18], position (relative orientation and/or distance) and genomic location (in gene deserts, introns and/or untranslated regions) [2]. Although sequence conservation between species can, in some cases, be an efficient predictor of enhancer identity, there are examples where genes with identical expression patterns in different species rely on enhancers that bear no similarities [19]. Within a single genome, however, sensitivity to DNase I a
%K enhancer
%K silencer
%K insulator
%K transcription factory
%K hub
%K long-range interactions
%K chromosome conformation capture
%K three-dimensional genome architecture
%U http://www.epigeneticsandchromatin.com/content/5/1/1