PT  - JOURNAL ARTICLE
AU  - Arnav Moudgil
AU  - Michael N. Wilkinson
AU  - Xuhua Chen
AU  - June He
AU  - Alex J. Cammack
AU  - Michael J. Vasek
AU  - Tomas Lagunas, Jr.
AU  - Zongtai Qi
AU  - Samantha A. Morris
AU  - Joseph D. Dougherty
AU  - Robi D. Mitra
TI  - Self-reporting transposons enable simultaneous readout of gene expression and transcription factor binding in single cells
AID  - 10.1101/538553
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 538553
4099  - http://biorxiv.org/content/early/2019/02/01/538553.short
4100  - http://biorxiv.org/content/early/2019/02/01/538553.full
AB  - In situ measurements of transcription factor (TF) binding are confounded by cellular heterogeneity and represent averaged profiles in complex tissues. Single cell RNA-seq (scRNA-seq) is capable of resolving different cell types based on gene expression profiles, but no technology exists to directly link specific cell types to the binding pattern of TFs in those cell types. Here, we present self-reporting transposons (SRTs) and their use in single cell calling cards (scCC), a novel assay for simultaneously capturing gene expression profiles and mapping TF binding sites in single cells. First, we show how the genomic locations of SRTs can be recovered from mRNA. Next, we demonstrate that SRTs deposited by the piggyBac transposase can be used to map the genome-wide localization of the TFs SP1, through a direct fusion of the two proteins, and BRD4, through its native affinity for piggyBac. We then present the scCC method, which maps SRTs from scRNA-seq libraries, thus enabling concomitant identification of cell types and TF binding sites in those same cells. As a proof-of-concept, we show recovery of cell type-specific BRD4 and SP1 binding sites from cultured cells. Finally, we map Brd4 binding sites in the mouse cortex at single cell resolution, thus establishing a new technique for studying TF biology in situ.