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Genomic views of distant-acting enhancers

Naturevolume 461, pages199–205 (2009)Cite this article

Abstract

In contrast to protein-coding sequences, the significance of variation in non-coding DNA in human disease has been minimally explored. A great number of recent genome-wide association studies suggest that non-coding variation is a significant risk factor for common disorders, but the mechanisms by which this variation contributes to disease remain largely obscure. Distant-acting transcriptional enhancers — a major category of functional non-coding DNA — are involved in many developmental and disease-relevant processes. Genome-wide approaches to their discovery and functional characterization are now available and provide a growing knowledge base for the systematic exploration of their role in human biology and disease susceptibility.

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Figure 1: Overview of gene regulation by distant-acting enhancers.
Figure 2: Consequences of deletion and mutation of the limb enhancer of sonic hedgehog.

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Acknowledgements

We thank M. Blow, S. Deutsch and A. Sczyrba for help with computational analysis of GWAS data and C. Attanasio for comments. L.A.P. and E.M.R. were supported by the Berkeley Program for Genomic Applications (funded by the US National Heart, Lung, and Blood Institute), and the Director, Office of Science, Office of Basic Energy Sciences, US Department of Energy, under contract number DE-AC02-05CH11231. L.A.P. was also supported by the US National Human Genome Research Institute.

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Authors and Affiliations

  1. Genomics Division, MS 84–171, Lawrence Berkeley National Laboratory, Berkeley, 94720, California, USA

    Axel Visel, Edward M. Rubin & Len A. Pennacchio

  2. US Department of Energy Joint Genome Institute, Walnut Creek, 94598, California, USA

    Axel Visel, Edward M. Rubin & Len A. Pennacchio

Authors
  1. Axel Visel
  2. Edward M. Rubin
  3. Len A. Pennacchio

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The authors declare no competing financial interests.

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Reprints and permissions information is available athttp://www.nature.com/reprints.

Correspondence should be addressed to L.A.P. (lapennacchio@lbl.gov).

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