Single-cell mapping of regulatory DNA-protein interactions.
| Publication Type | Academic Article |
| Authors | Chi W, Yoon S, Goksel E, Mekerishvili L, Pelt J, Lin Y, Prieto T, Zinno J, Ganesan S, Potenski C, Izzo F, Landau D, Raimondi I |
| Journal | Cell |
| Volume | 189 |
| Issue | 12 |
| Pagination | 3801-3816.e11 |
| Date Published | 06/04/2026 |
| ISSN | 1097-4172 |
| Keywords | Single-Cell Analysis, Transcription Factors, DNA-Binding Proteins, DNA |
| Abstract | Gene expression is controlled by transcription factors (TFs), whose genome binding is shaped by chromatin accessibility and histone modifications, yet mapping these interactions, particularly those with weak affinity or a transient nature, in single cells remains technically challenging. To address this gap, we developed docking and deamination followed by sequencing (D&D-seq), a single-cell immuno-tethering technology for profiling DNA-protein interactions. D&D-seq couples an antibody-binding nanobody to a cytosine base editor, a combination that enables detection of weak or transient factor binding through targeted cytosine-to-uracil editing at protein-bound genomic sites. This approach is compatible with standard single-cell multi-omic workflows and therefore allows integrated analyses of gene regulation. Using assay for transposase-accessible chromatin using sequencing (ATAC-seq) and single-cell ATAC-seq (scATAC-seq), we assessed chromatin accessibility as a functional readout of TF activity, and by coupling D&D-seq with whole-genome sequencing, we captured CTCF binding in both active and inactive chromatin compartments. |
| DOI | 10.1016/j.cell.2026.05.014 |
| PubMed ID | 42242226 |
| PubMed Central ID | PMC13366695 |