ArticleNature communications2026
A combinatorial domain screening platform reveals epigenetic effector interactions for transcriptional perturbation.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- A systematic comparison of single-cell perturbation response prediction models.Science advances · 2026Article
- Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.bioRxiv : the preprint server for biology · 2026Article
- Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026Review
- Clinical translation of epigenome editing technologies.Current opinion in biomedical engineering · 2026Article
- Next generation technologies for CRISPR-based epigenome and transcriptional modulation.Current opinion in biomedical engineering · 2026Article
- A toolkit for programmable transcriptional engineering across eukaryotic kingdoms.bioRxiv : the preprint server for biology · 2026Article
- CRISPR Epigenome Editing in Human Cells using Plasmid DNA Transfection and mRNA Nucleofection Delivery.Journal of visualized experiments : JoVE · 2025Article
- Utilizing small molecules to probe and harness the proteome by pooled protein tagging with ligandable domains.Frontiers in pharmacology · 2025Review
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Authors and funding
7 authors.
Funding
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Abstract
Epigenetic regulation involves the coordinated interplay of diverse proteins. To systematically explore these combinations, we present COMBINE (combinatorial interaction exploration), a high-throughput platform that tests over 50,000 pairs of epigenetic effector domains up to 2,094 amino acids in length for their ability to modulate endogenous human gene transcription. COMBINE reveals diverse synergistic interactions between epigenetic protein domains, including a potent KRAB-L3MBTL3 fusion that increases the effective targeting window, enhances gene silencing in dose-limited conditions, and enables robust dual-directional CRISPR perturbation. Inducible screening shows DNA methylation modifiers are essential for epigenetic memory, with distinct combinations driving long-term repression and activation. This systematic analysis of pairwise domain interactions advances our understanding of epigenetic crosstalks and the development of next-generation epigenome editing tools. More broadly, COMBINE offers a generalizable platform to functionally characterize combinatorial biological processes at scale.
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Registered trials
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