Gene expression is governed by epigenomic landscapes comprising transcription factor (TF) or chromatin remodeler (CR) binding. These networks are often disrupted in aging and disease, yet profiling DNA:Protein interactions across diverse cell types and states remains challenging. To address this, we developed D&D-seq, a single-cell immuno-tethering DNA:Protein mapping technology. By coupling species-specific antibody-binding nanobodies to a cytosine base editing enzyme, D&D-seq induces cytosine-to-uracil edits at protein-bound genomic regions, enabling multimodal single-cell analyses with high specificity. We profiled binding of six TFs and one CR in bulk, and validated single-cell CTCF and GATA binding. D&D-seq identified CTCF binding sites in primary human peripheral blood mononuclear cells, and combined with single-cell genotyping, revealed altered CTCF binding in IDH2-mutant hematopoietic cells. This approach expands the scope of single-cell multiomics, enabling direct mapping of TF and chromatin remodeler binding, advancing our understanding of gene regulation in health and disease.