Visel_2009: Genomic Views of Distant-Acting Enhancers


Enhancer Hedgehog (Hh) signaling pathway

Genomic Views of Distant-Acting Enhancers


In contrast to changes in protein-coding sequences, the significance of noncoding DNA variation in human disease has been minimally explored.

Distant-acting transcriptional enhancers - a major category of functional noncoding DNA - are likely involved in many developmental and disease-relevant processes.


genome-wide association studies (GWASs) have revealed a large number of disease susceptibility regions that do not overlap protein-coding genes, but rather map to noncoding intervals

a 58kb linkage disequilibrium block located at human chromosome 9p21 was shown to be reproducibly associated with an increased risk for coronary artery disease

But it lies 6kb away from the nearest known protein coding gne

To estimate the global contribution of variation in non-coding sequences to phenotypic and disease traits

One possibility that could explain these GWAS hits is that the non-coding intervals contain enhancers

Figure 1. Schematic overview of gene regulation by distant-acting enhancers

Transcriptional enhancers represent regulatory sequences that can be located

In vertebrates, enhancer sequences are thought to represent densely clustered aggregations of Transcription Factor binding sites

In-depth studies of individual genes such as APOE or NKX2-5   gene

driving distinct aspects of the mRNA expression pattern

In this review we will focus on the role of enhancers and on strategies to define their location and function genome-wide

Though they expect noncoding RNAs to play a role in human disease

Enhancers in Human Disease