ArticleNature biotechnology2025
Development of compact transcriptional effectors using high-throughput measurements in diverse contexts.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- CRISPR Technologies in Type 2 Diabetes: From Mechanistic Insights to Therapeutic Discovery.International journal of molecular sciences · 2026Review
- TIGRa: An ultra-compact programmable activator enabling multiplexed and efficient gene regulation.Cell stem cell · 2026Article
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
- Single-cell chromatin state transitions during epigenetic memory formation.Science advances · 2026Article
- Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.bioRxiv : the preprint server for 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
- Clinical translation of epigenome editing technologies.Current opinion in biomedical engineering · 2026Article
- Rewriting the epigenome: CRISPR tools for biological discovery and therapeutics.Current opinion in biomedical engineering · 2026Article
- A novel reaction-diffusion architecture for engineering self-organized patterns in mammalian cells.bioRxiv : the preprint server for biology · 2026Article
- Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits.bioRxiv : the preprint server for biology · 2026Article
- Simultaneous orthogonal cell engineering by a single CRISPR-Cas9 polyfunctional editor.Nature communications · 2026Article
- Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026Review
- A combinatorial domain screening platform reveals epigenetic effector interactions for transcriptional perturbation.Nature communications · 2026Article
- Miniature and versatile genome regulation TnpB-ωRNA toolkits facilitate cancer immunotherapy.Nature communications · 2026Article
- Systematic transcriptome analysis reveals the function of alternative promoters in hematopoietic lineages.Stem cell reports · 2026Article
- A toolkit for programmable transcriptional engineering across eukaryotic kingdoms.bioRxiv : the preprint server for biology · 2026Article
- Efficient clustered, regularly interspaced short palindromic repeats-based gene activation using combinatorial human transcription activation domains.Protein & cell · 2026Article
- Article
- Bifunctional transcriptional effector domains control gene expression pulses in an occupancy-dependent manner.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
26 authors.
Funding
Abstract
Transcriptional effectors are protein domains known to activate or repress gene expression; however, a systematic understanding of which effector domains regulate transcription across genomic, cell type and DNA-binding domain (DBD) contexts is lacking. Here we develop dCas9-mediated high-throughput recruitment (HT-recruit), a pooled screening method for quantifying effector function at endogenous target genes and test effector function for a library containing 5,092 nuclear protein Pfam domains across varied contexts. We also map context dependencies of effectors drawn from unannotated protein regions using a larger library tiling chromatin regulators and transcription factors. We find that many effectors depend on target and DBD contexts, such as HLH domains that can act as either activators or repressors. To enable efficient perturbations, we select context-robust domains, including ZNF705 KRAB, that improve CRISPRi tools to silence promoters and enhancers. We engineer a compact human activator called NFZ, by combining NCOA3, FOXO3 and ZNF473 domains, which enables efficient CRISPRa with better viral delivery and inducible control of chimeric antigen receptor T cells.
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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 Socratic graph.