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Nat Methods. 2013 Aug;10(8):774-80. doi: 10.1038/nmeth.2558. Epub 2013 Jul 14.

Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos.

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Department of Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.


Transcriptional enhancers are a primary mechanism by which tissue-specific gene expression is achieved. Despite the importance of these regulatory elements in development, responses to environmental stresses and disease, testing enhancer activity in animals remains tedious, with a minority of enhancers having been characterized. Here we describe 'enhancer-FACS-seq' (eFS) for highly parallel identification of active, tissue-specific enhancers in Drosophila melanogaster embryos. Analysis of enhancers identified by eFS as being active in mesodermal tissues revealed enriched DNA binding site motifs of known and putative, previously uncharacterized mesodermal transcription factors. Naive Bayes classifiers using transcription factor binding site motifs accurately predicted mesodermal enhancer activity. Application of eFS to other cell types and organisms should accelerate the cataloging of enhancers and understanding how transcriptional regulation is encoded in them.

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