2013年7月28日
Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model
Nature Genetics
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- 巻
- 45
- 号
- 9
- 開始ページ
- 1021
- 終了ページ
- 1028
- DOI
- 10.1038/ng.2713
Despite continual progress in the cataloging of vertebrate regulatory elements, little is known about their organization and regulatory architecture. Here we describe a massively parallel experiment to systematically test the impact of copy number, spacing, combination and order of transcription factor binding sites on gene expression. A complex library of ∼5,000 synthetic regulatory elements containing patterns from 12 liver-specific transcription factor binding sites was assayed in mice and in HepG2 cells. We find that certain transcription factors act as direct drivers of gene expression in homotypic clusters of binding sites, independent of spacing between sites, whereas others function only synergistically. Heterotypic enhancers are stronger than their homotypic analogs and favor specific transcription factor binding site combinations, mimicking putative native enhancers. Exhaustive testing of binding site permutations suggests that there is flexibility in binding site order. Our findings provide quantitative support for a flexible model of regulatory element activity and suggest a framework for the design of synthetic tissue-specific enhancers. © 2013 Nature America, Inc. All rights reserved.
- リンク情報
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- DOI
- https://doi.org/10.1038/ng.2713
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/23892608
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775494
- URL
- http://europepmc.org/abstract/med/23892608
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84883457107&origin=inward
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84883457107&origin=inward
- ID情報
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- DOI : 10.1038/ng.2713
- ISSN : 1061-4036
- eISSN : 1546-1718
- ORCIDのPut Code : 67786455
- PubMed ID : 23892608
- PubMed Central 記事ID : PMC3775494
- SCOPUS ID : 84883457107