Figure 59.

Schematic overview of a screening platform based on DNA-barcoded nucleosome libraries. Recombinant and semisynthetic histones are refolded into >50 different octamers in parallel, and assembled into mononucleosomes with barcoded DNA. Upon pooling, aliquots of the library are subjected to biochemical assays involving a pull-down step to enrich variants that exhibit certain traits. Subsequently, nucleosomal DNA is isolated and analyzed by next generation sequencing to provide a semiquantitative readout of hundreds to thousands of experiments.