TY - JOUR T1 - A viral toolkit for recording transcription factor-DNA interactions in live mouse tissues JF - bioRxiv DO - 10.1101/538504 SP - 538504 AU - Alexander J. Cammack AU - Arnav Moudgil AU - Tomas Lagunas AU - Jiayang Chen AU - Michael J. Vasek AU - Mark Shabsovich AU - Katherine McCullough AU - June He AU - Xuhua Chen AU - Misha Hooda AU - Michael N. Wilkinson AU - Timothy M. Miller AU - Robi D. Mitra AU - Joseph D. Dougherty Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/10/17/538504.abstract N2 - Transcription factors (TFs) enact precise regulation of gene expression through site-specific, genome-wide binding. Common methods for TF occupancy profiling, such as chromatin immunoprecipitation, are limited by requirement of TF-specific antibodies and provide only endpoint snapshots of TF binding. Alternatively, TF-tagging techniques, in which a TF is fused to a DNA-modifying enzyme that marks TF binding events across the genome as they occur, do not require TF-specific antibodies and offer the potential for unique applications, such as recording of TF occupancy over time and cell type-specificity through conditional expression of the TF-enzyme fusion. Here we create a viral toolkit for one such method, calling cards, and demonstrate that these reagents can be delivered to the live mouse brain and used to report TF occupancy. Further, we establish a Cre-dependent calling cards system, termed Flip-Excision (FLEX) calling cards and, in proof-of-principle experiments, show utility in defining cell type-specific TF profiles and recording and integrating TF binding events across time. This versatile approach will enable unique studies of TF-mediated gene regulation in live animal models. ER -