Jul 6, 2014

Using targeted chromatin regulators to engineer combinatorial and spatial transcriptional regulation

Cell
Albert J KeungAhmad S Khalil

Abstract

The transcription of genomic information in eukaryotes is regulated in large part by chromatin. How a diverse array of chromatin regulator (CR) proteins with different functions and genomic localization patterns coordinates chromatin activity to control transcription remains unclear. Here, we take a synthetic biology approach to decipher the complexity of chromatin regulation by studying emergent transcriptional behaviors from engineered combinatorial, spatial, and temporal patterns of individual CRs. We fuse 223 yeast CRs to programmable zinc finger proteins. Site-specific and combinatorial recruitment of CRs to distinct intralocus locations reveals a range of transcriptional logic and behaviors, including synergistic activation, long-range and spatial regulation, and gene expression memory. Comparing these transcriptional behaviors with annotated CR complex and function terms provides design principles for the engineering of transcriptional regulation. This work presents a bottom-up approach to investigating chromatin-mediated transcriptional regulation and introduces chromatin-based components and systems for synthetic biology and cellular engineering.

  • References45
  • Citations40

Citations

Mentioned in this Paper

Pathologic Cytolysis
Tetracycline Antibiotics
Saccharomyces cerevisiae Proteins
Establishment and Maintenance of Localization
Zinc Fingers
Real-Time Polymerase Chain Reaction
Protease Inhibitors [MoA]
Tetracyclines
Flow Cytometry
Meniscus structure of joint

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