Cellular heterogeneity confounds in situ assays of transcription factor (TF) binding. Single-cell RNA sequencing (scRNA-seq) deconvolves cell types from gene expression, but no technology links cell identity to TF binding sites (TFBS) in those cell types. We present self-reporting transposons (SRTs) and use them in single-cell calling cards (scCC), a novel assay for simultaneously measuring gene expression and mapping TFBS in single cells. The genomic locations of SRTs are recovered from mRNA, and SRTs deposited by exogenous, TF-transposase fusions can be used to map TFBS. We then present scCC, which map SRTs from scRNA-seq libraries, simultaneously identifying cell types and TFBS in those same cells. We benchmark multiple TFs with this technique. Next, we use scCC to discover BRD4-mediated cell-state transitions in K562 cells. Finally, we map BRD4 binding sites in the mouse cortex at single-cell resolution, establishing a new method for studying TF biology in situ. Moudgil et al. present a single-cell method for simultaneously capturing gene expression and transcription factor binding site data from the same cells, first in cell lines and then in the mouse brain.

Original languageEnglish
Pages (from-to)992-1008.e21
Issue number4
StatePublished - Aug 20 2020


  • bromodomains
  • calling cards
  • cell state
  • mouse cortex
  • single cell
  • transcription factors
  • transposons


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