Enhancer

In molecular biology, an enhancer is a DNA sequence that promotes the transcription of a gene (gene activity). In principle, an enhancer is a gene segment that ensures that a certain gene is transcribed more strongly. Enhancers can be located within genes, in intragenic regions and even on different chromosomes (Lewis MW et Al: 2019).

The advent of next-generation sequencing technologies has enabled the comprehensive identification of enhancers across the genome. Current estimates suggest over 400,000 enhancers distributed across the genome (Lewis MW et Al: 2019). The interactions between enhancers and their target genes are not exclusive; promoters often interact with multiple enhancers and vice versa. Enhancers are highly cell type-specific, so not all potential enhancers are active at the same time. Rather, there are tens of thousands of active enhancers in each cell type that control lineage-specific gene expression.

The transcription performance of a cell is largely determined by the active enhancer elements contained in its genome. Enhancers were first described in the 1980s as DNA sequences that increase the expression of a linked gene independent of its distance and orientation (Moreau P et al. 1981)

Enhancer dysfunction is increasingly emerging as an important factor in human disease, including cancer. A growing body of evidence from different tumor types shows that enhancer networks are restructured by molecular aberrations, collectively leading to the cancer phenotype (Sur I et al. 2016) . Translocations, deletions and mutations in regulatory genomic regions are frequently observed in cancer patients and can lead to loss of expression of tumor suppressors or overexpression of oncogenes (Lewis MW et Al: 2019). For example, genomic translocations in Burkitt's lymphoma shift the highly active enhancers of immunoglobulin heavy chain genes to the vicinity of the MYC oncogene, leading to deleterious activation of MYC expression.

In B-cell lymphoma, rearrangements and duplications of benign enhancers drive the expression of typical cancer genes such as MYC, BCL2 and NOTCH1 (Ryan RJ et al. 2015). In addition to translocation or duplication of enhancers, cell type-specific enhancers can also be activated or "hijacked" by cancer cells to activate genes that lead to tumorigenesis or drug resistance. The increasing importance of enhancers in disease pathogenesis has brought the elucidation of their functional mechanisms to the forefront. Although many common features of enhancers have been described over the years, the sequence of events involved in their activation remains unknown.

A well-known example of an enhancer is the so-called "LCR" (Locus Control Region), which regulates gene expression in the beta-globulin locus. Another example is an enhancer for the insulin gene. There are therefore specific enhancers in different genes that ensure that they are read more efficiently.

Enhancer-derived RNAs are referred to as eRNAs. They represent a group of RNAs that are transcribed by RNA polymerase II from the domain of transcriptional enhancers. eRNAs represent an important type of cis-regulatory element in the genome. eRNAs. They also serve as markers for the global identification of enhancers.

1. Lewis MW et Al: (2019) Transcriptional control by enhancers and enhancer RNAs. Transcription 10(4-5):171-186.
2. Liu F (2017) Enhancer-derived RNA: A Primer. Genomics Proteomics Bioinformatics 15:196-200.
3. Moreau P et al. (1981) The SV40 72 base repair repeat has a striking effect on gene expression both in SV40 and other chimeric recombinants. Nucleic Acids Res 9:6047-6068.
4. Ryan RJ et al. (2015) Detection of Enhancer-Associated Rearrangements Reveals Mechanisms of Oncogene Dysregulation in B-cell Lymphoma. Cancer Discov 5:1058-1071.
5. Sur I et al. (2016) The role of enhancers in cancer. Nat Rev Cancer 16:483-93