Abstract 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.
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