High-resolution analysis of DNA regulatory elements by synthetic saturation mutagenesis

Nat Biotechnol. 2009 Dec;27(12):1173-5. doi: 10.1038/nbt.1589.


We present a method that harnesses massively parallel DNA synthesis and sequencing for the high-throughput functional analysis of regulatory sequences at single-nucleotide resolution. As a proof of concept, we quantitatively assayed the effects of all possible single-nucleotide mutations for three bacteriophage promoters and three mammalian core promoters in a single experiment per promoter. The method may also serve as a rapid screening tool for regulatory element engineering in synthetic biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Base Sequence
  • DNA / chemistry*
  • DNA / genetics*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed / methods*
  • Regulatory Elements, Transcriptional / genetics*
  • Sequence Analysis, DNA / methods*


  • DNA