High-throughput and quantitative assessment of enhancer activity in mammals by CapStarr-seq

Cell-type specific regulation of gene expression requires the activation of promoters by distal genomic elements defined as enhancers. The identification and the characterization of enhancers are challenging in mammals due to their genome complexity. Here we develop CapStarr-Seq, a novel high-throug...

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Bibliographic Details
Published in:Nature communications 2015-04, Vol.6 (1), p.6905-6905, Article 6905
Main Authors: Vanhille, Laurent, Griffon, Aurélien, Maqbool, Muhammad Ahmad, Zacarias-Cabeza, Joaquin, Dao, Lan T.M., Fernandez, Nicolas, Ballester, Benoit, Andrau, Jean Christophe, Spicuglia, Salvatore
Format: Article
Language:English
Subjects:
631/1647/1407/2163
631/45/612/822
631/61/212/177
631/61/514/1948
Animals
Chromatin Immunoprecipitation
Enhancer Elements, Genetic - genetics
Gene Expression - genetics
Gene Expression Regulation - genetics
High-Throughput Nucleotide Sequencing - methods
Humanities and Social Sciences
Life Sciences
Male
Mice
multidisciplinary
NIH 3T3 Cells
Promoter Regions, Genetic - genetics
Science
Science (multidisciplinary)
Sequence Analysis, DNA - methods
Transcription Factors - genetics
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Summary:Cell-type specific regulation of gene expression requires the activation of promoters by distal genomic elements defined as enhancers. The identification and the characterization of enhancers are challenging in mammals due to their genome complexity. Here we develop CapStarr-Seq, a novel high-throughput strategy to quantitatively assess enhancer activity in mammals. This approach couples capture of regions of interest to previously developed Starr-seq technique. Extensive assessment of CapStarr-seq demonstrates accurate quantification of enhancer activity. Furthermore, we find that enhancer strength is associated with binding complexity of tissue-specific transcription factors and super-enhancers, while additive enhancer activity isolates key genes involved in cell identity and function. The CapStarr-Seq thus provides a fast and cost-effective approach to assess the activity of potential enhancers for a given cell type and will be helpful in decrypting transcription regulation mechanisms. Characterizing mammalian gene expression regulation by enhancer elements is complicated by the size and complexity of the genome. Here Vanhille et al. demonstrate CapStarr-Seq, a novel high-throughput method for assessing potential enhancers and deciphering the mechanisms regulating transcription
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms7905