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We develop a method called open chromatin enrichment and network Hi-C (OCEAN-C) for antibody-independent mapping of global open chromatin interactions. By integrating FAIRE-seq and Hi-C, OCEAN-C detects open chromatin interactions enriched by active cis-regulatory elements. | Li et al. Genome Biology 2018 19 54 https doi.org 10.1186 s13059-018-1430-4 METHOD Open Access OCEAN-C mapping hubs of open chromatin interactions across the genome reveals gene regulatory networks Tingting Li1 2 Lumeng Jia1 Yong Cao1 Qing Chen1 and Cheng Li1 3 Abstract We develop a method called open chromatin enrichment and network Hi-C OCEAN-C for antibody-independent mapping of global open chromatin interactions. By integrating FAIRE-seq and Hi-C OCEAN-C detects open chromatin interactions enriched by active cis-regulatory elements. We identify more than 10 000 hubs of open chromatin interactions HOCIs in human cells which are mainly active promoters and enhancers bound by many DNA-binding proteins and form interaction networks crucial for gene transcription. In addition to identifying large-scale topological structures including topologically associated domains and A B compartments OCEAN-C can detect HOCI-mediated chromatin interactions that are strongly associated with gene expression super-enhancers and broad H3K4me3 domains. Background PLAC-seq 21 . In particular DNase-C identifies high- The local chromatin conformation regulates gene tran- confidence DNA contacts at kilobase resolution by using scriptional activity through facilitating interactions be- DNase I to digest the genome DNA instead of restriction tween promoters and distant active regulatory elements enzymes 16 22 . These techniques have greatly advanced such as enhancers repressors and silencers 1 2 . These our understanding of detailed features of the genome 3D cis-regulatory elements are loosely packed and relatively structure and regulation of the genome 6 23 26 . How- free of nucleosomes which are necessary for transcrip- ever ChIA-PET HiChIP and PLAC-seq only determine tion factors and other regulatory proteins to gain access the subset of interactions mediated by specific DNA- to DNA 3 5 . Traditionally active regulatory elements binding proteins whereas Hi-C captures all genomic in- .