D&D-seq: A single-cell immuno-tethering method for mapping weak DNA-protein interactions
This article presents D&D-seq (docking and deamination followed by sequencing), a novel single-cell immuno-tethering technology developed to map DNA-protein interactions, particularly weak or transient transcription factor (TF) binding events that are difficult to detect with existing methods. The technique couples an antibody-binding nanobody to a cytosine base editor, enabling genome-wide analysis of transcription factor binding across different chromatin states at single-cell resolution. This addresses a key technical gap in understanding how gene expression is controlled by transcription factors whose genome binding is shaped by chromatin accessibility and histone modifications.
Key quotes
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
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