APA
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Tycko, J., DelRosso, N., Hess, G. T., Aradhana, Banerjee, A., Mukund, A., … Bintu#, L. (2020). High-Throughput Discovery and Characterization of Human Transcriptional Effectors. Cell.
Chicago/Turabian
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Tycko, Josh, Nicole DelRosso, Gaelen T. Hess, Aradhana, A. Banerjee, Aditya Mukund, Mike V. Van, et al. “High-Throughput Discovery and Characterization of Human Transcriptional Effectors.” Cell (2020).
MLA
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Tycko, Josh, et al. “High-Throughput Discovery and Characterization of Human Transcriptional Effectors.” Cell, 2020.
BibTeX Click to copy
@article{josh2020a,
title = {High-Throughput Discovery and Characterization of Human Transcriptional Effectors},
year = {2020},
journal = {Cell},
author = {Tycko, Josh and DelRosso, Nicole and Hess, Gaelen T. and Aradhana and Banerjee, A. and Mukund, Aditya and Van, Mike V. and Ego, Braeden K. and Yao, David and Spees, Kaitlyn K. and Suzuki, Peter H. and Marinov, G. and Kundaje, A. and Bassik#, M. and Bintu#, Lacramioara}
}
Thousands of proteins localize to the nucleus; however, it remains unclear which contain transcriptional effectors. Here, we develop HT-recruit - a pooled assay where protein libraries are recruited to a reporter, and their transcriptional effects are measured by sequencing. Using this approach, we measure gene silencing and activation for thousands of domains. We find a relationship between repressor function and evolutionary age for the KRAB domains, discover Homeodomain repressor strength is collinear with Hox genetic organization, and identify activities for several Domains of Unknown Function. Deep mutational scanning of the CRISPRi KRAB maps the co-repressor binding surface and identifies substitutions that improve stability/silencing. By tiling 238 proteins, we find repressors as short as 10 amino acids. Finally, we report new activator domains, including a divergent KRAB. Together, these results provide a resource of 600 human proteins containing effectors and demonstrate a scalable strategy for assigning functions to protein domains.
