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DNA elements

The ins and outs of enhancer validation

Nature Reviews Genetics volume 18, page 3 (2017)Cite this article

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A caveat of existing approaches for the identification of candidate regulatory sequences in mammalian genomes is that enhancer elements are predicted indirectly; for example, based on antibody binding to epigenomic modifications or transcription factors in the case of chromatin immunoprecipitation followed by sequencing (ChIP-seq). Functional validation is often done using episomal reporter assays, in which a candidate enhancer sequence is inserted next to a minimal promoter that drives expression of a reporter gene and tested in an episomal manner (that is, without integrating into the genome). Multiplexing of these reporter assays by sequencing-based quantification of reporter barcodes in massively parallel reporter assays (MPRAs) have made this approach high-throughput.

In a systematic investigation, Inoue et al. set out to determine to what extent the episomal context in reporter assays can confound the functional validation of candidate enhancers. To this end, the functional activities of 2,236 potential liver enhancer sequences and 204 control sequences were compared in a chromosomally integrated versus an episomal context.

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References

  1. Inoue, F. et al. A systematic comparison reveals substantial differences in chromosomal versus episomal encoding of enhancer activity. Genome Res. http://dx.doi.org/10.1101/gr.212092.116 (2016)

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Authors
  1. Linda Koch
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Koch, L. The ins and outs of enhancer validation. Nat Rev Genet 18, 3 (2017). https://doi.org/10.1038/nrg.2016.155

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