Multiplexed programmable release of captured DNA.

ABSTRACT

Nucleic-acid hybridization is widely used for the specific capture of complementary sequences from complex samples. It is useful for both analytical methodologies, such as array hybridization (e.g. transcriptome analysis, genetic-variation analysis), and preparative strategies such as exome sequencing and sequence-specific proteome capture and analysis (PICh, HyCCAPP). It has not generally been possible to selectively elute particular captured subsequences, however, as the conditions employed for disruption of a duplex can lack the specificity needed to discriminate between different sequences. We show here that it is possible to bind and selectively release multiple sets of sequences by using toehold-mediated DNA branch migration. The strategy is illustrated for simple mixtures of oligonucleotides, for the sequence-specific capture and specific release of crosslinked yeast chromatin, and for the specific release of oligonucleotides hybridized to DNA microarrays.