Enhancers, enhancers – from their discovery to today’s universe of transcription enhancers

Abstract

Transcriptional enhancers are short (200-1500 base pairs) DNA segments that are able to dramatically boost transcription from the promoter of a target gene. Originally discovered in simian virus 40 (SV40), a small DNA virus, transcription enhancers were soon also found in immunoglobulin genes and other cellular genes as key determinants of cell-type-specific gene expression. Enhancers can exert their effect over long distances of thousands, even hundreds of thousands of base pairs, either from upstream, downstream, or from within a transcription unit. The number of enhancers in eukaryotic genomes correlates with the complexity of the organism; a typical mammalian gene is likely controlled by several enhancers to fine-tune its expression at different developmental stages, in different cell types and in response to different signaling cues. Here, I provide a personal account of how enhancers were discovered more than 30 years ago, and also address the amazing development of the field since then.

Widespread changes in nucleosome accessibility without changes in nucleosome occupancy during a rapid transcriptional induction

“…2). Enhancer regions were reported to be nucleosome-depleted when active (Schaffner 2015), so we examined whether nucleosomes were lost from up-regulated enhancers. We defined up-regulated enhancers as regions that show an increase in H3K27ac levels at least twofold at time intervals 0-1 h and 1-4 h and are distinct from promoters of annotated genes (located outside the regions from −1 kb to +0.5 kb of the TSS).…”

Ever-Changing Landscapes: Transcriptional Enhancers in Development and Evolution

“…Much of this information is encoded by cis-regulatory elements called enhancers, canonically defined as short (~100-1000bp) noncoding DNA sequences that act to drive transcription independent of their relative distance, location or orientation to their cognate promoter (for a historical perspective on the discovery of enhancers, see Schaffner, 2015). Although enhancers share many features with other classes of cis-regulatory elements, especially promoters (reviewed in (Kim and Shiekhattar, 2015)), it is their ability to activate transcription over long genomic distances that sets them apart.…”

Identification of Novel Gata3 Distal Enhancers Active in Mouse Embryonic Lens

“…Many key developmental genes are regulated by a combination of proximal (i.e., promoter) and distal regulatory elements such as enhancers (Long et al, 2016). Enhancers are defined as relatively short (100-1000 bp) DNA sequences that can activate transcription from one or more cognate promoters over long genomic distances (Schaffner, 2015;Kim and Shiekhattar, 2015). Chromatin of active enhancers is marked by a combination of H3K4me1-and H3K27ac-modified core histone H3 proteins (Long et al, 2016).…”