All Publications

  • High-throughput functional characterization of combinations of transcriptional activators and repressors. Cell systems Mukund, A. X., Tycko, J., Allen, S. J., Robinson, S. A., Andrews, C., Sinha, J., Ludwig, C. H., Spees, K., Bassik, M. C., Bintu, L. 2023

    Abstract

    Despite growing knowledge of the functions of individual human transcriptional effector domains, much less is understood about how multiple effector domains within the same protein combine to regulate gene expression. Here, we measure transcriptional activity for 8,400 effector domain combinations by recruiting them to reporter genes in human cells. In our assay, weak and moderate activation domains synergize to drive strong gene expression, whereas combining strong activators often results in weaker activation. In contrast, repressors combine linearly and produce full gene silencing, and repressor domains often overpower activation domains. We use this information to build a synthetic transcription factor whose function can be tuned between repression and activation independent of recruitment to target genes by using a small-molecule drug. Altogether, we outline the basic principles of how effector domains combine to regulate gene expression and demonstrate their value in building precise and flexible synthetic biology tools. A record of this paper's transparent peer review process is included in the supplemental information.

    View details for DOI 10.1016/j.cels.2023.07.001

    View details for PubMedID 37543039

  • CRISPR-Suppressor Scanning Unsticks Molecular Glues. ACS central science Robinson, S. A., Banik, S. M. 2022; 8 (4): 408-411

    View details for DOI 10.1021/acscentsci.2c00216

    View details for PubMedID 35505876