ArticleCell systems2023
High-throughput functional characterization of combinations of transcriptional activators and repressors.
Article in Cell systems, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- A transcription factor by any other name - function beyond DNA binding and transactivation.EMBO reports · 2026Review
- Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity.Genome biology · 2026Article
- High-throughput measurements of protein domain functions using magnetic separation.Nature protocols · 2026Review
- Next generation technologies for CRISPR-based epigenome and transcriptional modulation.Current opinion in biomedical engineering · 2026Article
- A combinatorial domain screening platform reveals epigenetic effector interactions for transcriptional perturbation.Nature communications · 2026Article
- UBIQUITOUS FUNCTIONAL SYNERGY PARTIALLY EXPLAINS WHY MOST TRANSCRIPTION FACTOR BINDING IS NON-FUNCTIONAL.bioRxiv : the preprint server for biology · 2026Article
- Elucidating the susceptibility genes between insomnia and migraine by integrating genetic data and transcriptomes.The journal of headache and pain · 2026Article
- Bifunctional transcriptional effector domains control gene expression pulses in an occupancy-dependent manner.bioRxiv : the preprint server for biology · 2025Article
- Combinatorial protein engineering identifies potent CRISPR activators with reduced toxicity.Nature communications · 2025Article
- Emergence of activation or repression in transcriptional control under a fixed molecular context.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Development of compact transcriptional effectors using high-throughput measurements in diverse contexts.Nature biotechnology · 2025Article
- Article
- Engineering novel CRISPRi repressors for highly efficient mammalian gene regulation.Genome biology · 2025Article
- Versatile roles of disordered transcription factor effector domains in transcriptional regulation.The FEBS journal · 2025Review
- Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.Molecular cell · 2025Article
- Engineered CRISPR-Cas12a for higher-order combinatorial chromatin perturbations.Nature biotechnology · 2025Article
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Combinatorial effector targeting (COMET) for transcriptional modulation and locus-specific biochemistry.bioRxiv : the preprint server for biology · 2024Article
- Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications.Cell chemical biology · 2024Review
- Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
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.