Evidence map›Paper›PMID 37552983›Full record

ArticleCell2023

Cooperative assembly confers regulatory specificity and long-term genetic circuit stability.

Meghan D J Bragdon, Nikit Patel, James Chuang, Ethan Levien, Caleb J Bashor, Ahmad S Khalil

Abstract read
In one paragraph

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  8. Review
  9. Multivalency Enables Signal Processing at Single Protein Level.Journal of the American Chemical Society · 2025
    Article
  10. Article
  11. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  12. Why cellular computations challenge our design principles.Seminars in cell & developmental biology · 2025
    Review
  13. Article
  14. Liquid condensates: a new barrier to loop extrusion?Cellular and molecular life sciences : CMLS · 2025
    Review
  15. Article
  16. Article
  17. Review
  18. Cyanamide-inducible expression of homing nucleaseSynthetic and systems biotechnology · 2024
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Meghan D J BragdonBiological Design Center, Boston University, Boston, MA 02215, USA; Program in Molecular Biology, Cell Biology and Biochemistry, Boston University, Boston, MA 02215, USA.
Nikit PatelBiological Design Center, Boston University, Boston, MA 02215, USA; Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
James ChuangDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Ethan LevienDepartment of Mathematics, Dartmouth College, Hanover, NH 03755, USA.
Caleb J BashorDepartment of Bioengineering, Rice University, Houston, TX 77030, USA; Department of Biosciences, Rice University, Houston, TX 77030, USA.
Ahmad S KhalilBiological Design Center, Boston University, Boston, MA 02215, USA; Program in Molecular Biology, Cell Biology and Biochemistry, Boston University, Boston, MA 02215, USA; Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. Electronic address: khalil@bu.edu.

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
ePACE: automation platforms for adaptable and scalable continuous evolution of biomolecules with therapeutic potentialR01EB027793 · NIBIB · BROAD INSTITUTE, INC. · PI Ahmad Samir Khalil, DAVID R LIU · 2019 to 2026
$6.1M
Synthetic toolkit for precision gene expression control and signal processing in mammalian cellsR01EB029483 · NIBIB · HARVARD UNIVERSITY · PI Ahmad Samir Khalil · 2020 to 2026
$5.0M
A synthetic signaling pathway engineering platform for creating precision cell-based sense-and-response devicesR01EB032272 · NIBIB · RICE UNIVERSITY · PI BASHOR, CALEB · 2021 to 2024
$1.4M
NHGRI NIH HHS RM1 HG009490NIBIB NIH HHS R01 EB027793NIBIB NIH HHS R01 EB029483NIBIB NIH HHS R01 EB032272
6 · The paper itself

Abstract

A ubiquitous feature of eukaryotic transcriptional regulation is cooperative self-assembly between transcription factors (TFs) and DNA cis-regulatory motifs. It is thought that this strategy enables specific regulatory connections to be formed in gene networks between otherwise weakly interacting, low-specificity molecular components. Here, using synthetic gene circuits constructed in yeast, we find that high regulatory specificity can emerge from cooperative, multivalent interactions among artificial zinc-finger-based TFs. We show that circuits "wired" using the strategy of cooperative TF assembly are effectively insulated from aberrant misregulation of the host cell genome. As we demonstrate in experiments and mathematical models, this mechanism is sufficient to rescue circuit-driven fitness defects, resulting in genetic and functional stability of circuits in long-term continuous culture. Our naturally inspired approach offers a simple, generalizable means for building high-fidelity, evolutionarily robust gene circuits that can be scaled to a wide range of host organisms and applications.

Indexed as

Gene Regulatory NetworksTranscription FactorsGenomeSaccharomyces cerevisiaeTranscription Factorscooperativityfitnessgene circuitsgene regulationmodelingspecificitysynthetic biologytranscription factoryeastzinc fingers

Identifiers

PMID37552983
PMCPMC10528910

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.