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Multiplex Chromatin Interaction Analysis with Single-Molecule Precision

Meizhen Zheng, Simon Zhongyuan Tian, Rahul Maurya, Byoungkoo Lee, Minji Kim, Daniel Capurso, Emaly Piecuch, Liang Gong, Jacqueline Jufen Zhu, Chee Hong Wong, Chew Yee Ngan, Ping Wang, Xiaoan Ruan, Chia-Lin Wei, Yijun Ruan
doi: https://doi.org/10.1101/252049
Meizhen Zheng
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Simon Zhongyuan Tian
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Rahul Maurya
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Byoungkoo Lee
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Minji Kim
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Daniel Capurso
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Emaly Piecuch
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
2Department of Genetics and Genome Sciences, University of Connecticut Health Center, 400 Farmington Avenue, Farmington, CT 06030, USA
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Liang Gong
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Jacqueline Jufen Zhu
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
2Department of Genetics and Genome Sciences, University of Connecticut Health Center, 400 Farmington Avenue, Farmington, CT 06030, USA
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Chee Hong Wong
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Chew Yee Ngan
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Ping Wang
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Xiaoan Ruan
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Chia-Lin Wei
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
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Yijun Ruan
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA
2Department of Genetics and Genome Sciences, University of Connecticut Health Center, 400 Farmington Avenue, Farmington, CT 06030, USA
3College of Informatics, Huazhong Agricultural University, Wuhan, Hubei 430070, China
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Abstract

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.

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Posted January 25, 2018.
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Multiplex Chromatin Interaction Analysis with Single-Molecule Precision
Meizhen Zheng, Simon Zhongyuan Tian, Rahul Maurya, Byoungkoo Lee, Minji Kim, Daniel Capurso, Emaly Piecuch, Liang Gong, Jacqueline Jufen Zhu, Chee Hong Wong, Chew Yee Ngan, Ping Wang, Xiaoan Ruan, Chia-Lin Wei, Yijun Ruan
bioRxiv 252049; doi: https://doi.org/10.1101/252049
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Multiplex Chromatin Interaction Analysis with Single-Molecule Precision
Meizhen Zheng, Simon Zhongyuan Tian, Rahul Maurya, Byoungkoo Lee, Minji Kim, Daniel Capurso, Emaly Piecuch, Liang Gong, Jacqueline Jufen Zhu, Chee Hong Wong, Chew Yee Ngan, Ping Wang, Xiaoan Ruan, Chia-Lin Wei, Yijun Ruan
bioRxiv 252049; doi: https://doi.org/10.1101/252049

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