Using Synthetic DNA Libraries to Investigate Chromatin and Gene Regulation

Holly Kleinschmidt, Cheng Xu, Lu Bai

Research output: Contribution to journalReview articlepeer-review


Despite the recent explosion in genome-wide studies in chromatin and gene regulation, we are still far from extracting a set of genetic rules that can predict the function of the regulatory genome. One major reason for this deficiency is that gene regulation is a multi-layered process that involves an enormous variable space, which cannot be fully explored using native genomes. This problem can be partially solved by introducing synthetic DNA libraries into cells, a method that can test the regulatory roles of thousands to millions of sequences with limited variables. Here, we review recent applications of this method to study transcription factor (TF) binding, nucleosome positioning, and transcriptional activity. We discuss the design principles, experimental procedures, and major findings from these studies and compare the pros and cons of different approaches.

Original languageEnglish (US)
Pages (from-to)167-189
Number of pages23
Issue number3
StatePublished - Sep 2023

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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