TransMPRA: A framework for assaying the role of manytrans-acting factors at many enhancers

Gene regulation occurs through trans -acting factors ( e.g. transcription factors) acting on cis -regulatory elements ( e.g. enhancers). Massively parallel reporter assays (MPRAs) functionally survey large numbers of cis -regulatory elements for regulatory potential, but do not identify the trans -acting factors that mediate any observed effects. Here we describe trans MPRA — a reporter assay that efficiently combines multiplex CRISPR-mediated perturbation and MPRAs to identify trans- acting factors that modulate the regulatory activity of specific enhancers.