Direct DNA crosslinking with CAP-C uncovers transcription-dependent chromatin organization at high resolution

We introduce Chemical-crosslinking Assisted Proximity Capture (CAP-C), a method that utilizes multi-functional chemical crosslinkers with defined physical sizes to directly assess spatial distances between nuclear genomic sequences. CAP-C avoids limitations caused by extensive protein-DNA crosslinking in most in situ methods, and thus generates chromatin contact maps at high resolution with low background noise. Overall design: CAP-C utilizes a multifunctional PAMAM dendrimer platform instead of DNA-bound proteins to crosslink spatially adjacent DNA sequences, followed by restriction digestion and proximal ligation and high-throughput sequencing. We develop this method to examine the chromatin architecture of mouse embryonic stem cell F123, human HCT116 and drosophila S2 cell lines.