ChIP-seq accurately predicts tissue-specific activity of enhancers

Axel Visel, Matthew J. Blow, Zirong Li, Tao Zhang, Jennifer A. Akiyama, Amy Holt, Ingrid Plajzer-Frick, Malak Shoukry, Crystal Wright, Feng Chen, Veena Afzal, Bing Ren, Edward M. Rubin and Len A. Pennacchio ()
Additional contact information
Axel Visel: MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Matthew J. Blow: MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Zirong Li: Ludwig Institute for Cancer Research, University of California San Diego (UCSD) School of Medicine, La Jolla, California 92093, USA
Tao Zhang: Walnut Creek, California 94598, USA
Jennifer A. Akiyama: MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Amy Holt: MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Ingrid Plajzer-Frick: MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Malak Shoukry: MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Crystal Wright: Walnut Creek, California 94598, USA
Feng Chen: Walnut Creek, California 94598, USA
Veena Afzal: MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Bing Ren: Ludwig Institute for Cancer Research, University of California San Diego (UCSD) School of Medicine, La Jolla, California 92093, USA
Edward M. Rubin: MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
Len A. Pennacchio: MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA

Nature, 2009, vol. 457, issue 7231, 854-858

Abstract: Abstract A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.

Date: 2009
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DOI: 10.1038/nature07730

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