Abstract
<jats:p> Interactions among <jats:italic>cis</jats:italic> -regulatory elements (CREs) are central to mammalian gene regulation. Long @$$ massively parallel reporter assays (LAMPRAs) integrate combinatorial cloning, molecular barcoding and long- and short-read sequencing, to scalably measure how CRE identities, numbers, spacings, orders, orientations, and interactions shape regulatory output at multi-kilobase length scales. As a proof-of-concept, we assay 36,000 x 5-kb synthetic <jats:italic>cis</jats:italic> -regulatory loci (sCRLs), each a 5 x 1-kb random combination of enhancers, insulators and spacers, to model how locus composition drives gene expression. </jats:p>