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Review
. 2015 Aug 27;162(5):948-59.
doi: 10.1016/j.cell.2015.08.008.

Architectural and Functional Commonalities between Enhancers and Promoters

Tae-Kyung Kim  1 , Ramin Shiekhattar  2
Affiliations
Review

Architectural and Functional Commonalities between Enhancers and Promoters

Tae-Kyung Kim et al. Cell. .

Abstract

With the explosion of genome-wide studies of regulated transcription, it has become clear that traditional definitions of enhancers and promoters need to be revisited. These control elements can now be characterized in terms of their local and regional architecture, their regulatory components, including histone modifications and associated binding factors, and their functional contribution to transcription. This Review discusses unifying themes between promoters and enhancers in transcriptional regulatory mechanisms.

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Figures

Figure 1
Figure 1. A contemporary view on promoters and enhancers
Features of promoters include: Transcription initiation in the sense and anti-sense direction is mediated by the transcription machinery assembled independently onto its own core promoter. Although not shown here, convergent transcription has been observed at the promoters of weakly expressed genes. H3K4me3 is highly enriched at the promoter regions. Enhancer-like chromatin signatures (H3K4me1 and H3K27ac) and the Tyr-1P form of the RNAPII have also been observed near the upstream anti-sense TSSs. Polyadenylation sites are enriched near the 3′ end of the upstream anti-sense RNAs and mediate the exosome-dependent degradation of the antisense RNAs. 5′ splice sites are only present in the coding gene, and might contribute to the productive elongation of sense mRNA transcripts through the binding of the U1 splicing complex, which blocks PAS-mediated early termination. The Ser-5P form of RNAPII is engaged in upstream anti-sense transcription, but it is not known if Ser-2P of RNAPII occurs during the elongation of anti-sense RNA. Features of enhancers include: Like the promoter, the enhancer recruits the general transcription factors (GTF) including RNAPII and initiates transcription at defined sites. Enhancer-driven transcription typically exhibits more prominent bi-directionality than that stemming from the promoter. H3K4me1/2 is commonly enriched at enhancers. Functionally active enhancers also exhibit a high level of H3K27 acetylation whereas poised or inactive enhancers are marked by H3K27me3. Ser-5P and Tyr-1P forms of the RNAPII have been observed. It is not clear whether or not Ser-2P RNAPII and H3K36me3 marks are present at active enhancers. 5′ splice site sequences are not enriched near the regions surrounding enhancers. Both strands of enhancer RNAs appear to be degraded by the exosome, although it is not known whether it is mediated by the PAS-dependent mechanism.
Figure 2
Figure 2. Mechanisms of enhancer-promoter interactions
H3K4me1/2 modification at enhancers can be mediated by RNAPII transcription activity. Enhancer RNA is also shown to play a role in various stages of transcription. Looping: The Mediator/Cohesin complex is involved in stable formation of enhancer-promoter looping. Some eRNAs (e.g., ncRNA-a, and eRNAs expressed from oestrogen receptor-α bound enhancers) facilitate the looping through an interaction with the subunit(s) of the Mediator/Cohesin complex. Chromatin remodeling: eRNAs (e.g., CERNA) can also promote transcription by remodeling the chromatin structure such that the accessibility of RNAPII machinery is increased. RNAPII transition: Early RNAPII elongation is another transcription step regulated by eRNAs. eRNAs (e.g., Arc eRNAs) can help RNAPII enter into a productive elongation stage by facilitating transient release of the negative elongation factor, NELF, which causes RNAPII pausing near the TSS.
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