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Review
. 2018 Apr 1;10(4):483-498.
doi: 10.2217/epi-2017-0157. Epub 2018 Mar 27.

Enhancer talk

Valentina Snetkova  1   2 , Jane A Skok  1
Affiliations
Review

Enhancer talk

Valentina Snetkova et al. Epigenomics. .

Abstract

Enhancers are short noncoding segments of DNA (100-1000 bp) that control the temporal and spatial activity of genes in an orientation-independent manner. They can be separated from their target genes by large distances and are thus known as distal regulatory elements. One consequence of the variability in the distance separating enhancers and their target promoters is that it is difficult to determine which elements are involved in the regulation of a particular gene. Moreover, enhancers can be found in clusters in which multiple regulatory elements control expression of the same target gene. However, little is known about how the individual elements contribute to gene expression. Here, we describe how chromatin conformation promotes and constraints enhancer activity. Further, we discuss enhancer clusters and what is known about the contribution of individual elements to the regulation of target genes. Finally, we examine the reliability of different methods used to identify enhancers.

Keywords: 3D conformation; CTCF; LCRs; TADs; chromatin contacts; cohesin; enhancers; stretch enhancers; super enhancers.

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Conflict of interest statement

Financial & competing interests disclosure

JA Skok is supported by NIH grant R35GM122515, 4P30CA016087-36 Cancer Center Support Grant NIH/NCI (Neel) and 2R01CA140729-06A1 NIH/NCI (Carroll). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Cell-type-specific transcription factors bind to both enhancers and promoters, recruiting co-activators, mediator complex and chromatin remodelers, all of which potentiate interaction between the regulatory elements and induce transcription.
TF: Transcripton factor.
<b>Figure 2.</b>
Figure 2.. Multiloop activation hubs of regulatory elements controlled by cell-type-specific transcription factors drive changes in 3D interactions and gene expression.
TF: Transcription factor.
<b>Figure 3.</b>
Figure 3.. Modes of cross talk between the individual elements in an enhancer cluster.
Enhancers in additive mode act autonomously from each other so that deletion of one element does not impact other enhancers. In a synergistic mode, neighboring enhancers influence each other's activity, so that deletion of one enhancer has an impact on the way other enhancers in the cluster control a target gene. The impact of enhancer deletion on a target gene transcription is shown by the size and intensity of gray arrows. Enhancers in the cluster can also repress neighboring regulatory elements.
<b>Figure 4.</b>
Figure 4.. The immunoglobulin kappa locus, Igk on murine chromosome 6 consists of multiple variable and joining segments followed by a constant region gene.
Igk expression and recombination are controlled by three enhancers: MiEκ, 3′Eκ and Edκ, which are clustered at the 3′ end of the gene. The three enhancers form a hub in the developing B cells. Deletion of either MiEκ or 3′Eκ limits interactions between the two remaining enhancers.
See this image and copyright information in PMC

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