RT Journal Article SR Electronic T1 Multiplex Chromatin Interaction Analysis with Single-Molecule Precision JF bioRxiv FD Cold Spring Harbor Laboratory SP 252049 DO 10.1101/252049 A1 Meizhen Zheng A1 Simon Zhongyuan Tian A1 Rahul Maurya A1 Byoungkoo Lee A1 Minji Kim A1 Daniel Capurso A1 Emaly Piecuch A1 Liang Gong A1 Jacqueline Jufen Zhu A1 Chee Hong Wong A1 Chew Yee Ngan A1 Ping Wang A1 Xiaoan Ruan A1 Chia-Lin Wei A1 Yijun Ruan YR 2018 UL http://biorxiv.org/content/early/2018/01/25/252049.abstract AB We describe a microfluidics-based strategy for genome-wide analysis of multiplex chromatin interactions with single-molecule precision. In multiplex chromatin interaction analysis (multi-ChIA), individual chromatin complexes are partitioned into droplets that contain a gel bead with unique DNA barcode, in which tethered chromatin DNA fragments are barcoded and amplified for sequencing and mapping to demarcate chromatin contacts. Thus, multi-ChIA has the unprecedented ability to uncover multiplex chromatin interactions at single-molecule level, which has been impossible using previous methods that rely on analyzing pairwise contacts via proximity ligation. We demonstrate that multiplex chromatin interactions predominantly contribute to topologically associated domains, and clusters of gene promoters and enhancers provide a fundamental topological framework for co-transcriptional regulation.