title: Constructing 3D interaction maps from 1D epigenomes.
abstract: The human genome is tightly packaged into chromatin whose functional output depends on both one-dimensional (1D) local chromatin states and three-dimensional (3D) genome organization. Currently, chromatin modifications and 3D genome organization are measured by distinct assays. An emerging question is whether it is possible to deduce 3D interactions by integrative analysis of 1D epigenomic data and associate 3D contacts to functionality of the interacting loci. Here we present EpiTensor, an algorithm to identify 3D spatial associations within topologically associating domains (TADs) from 1D maps of histone modifications, chromatin accessibility and RNA-seq. We demonstrate that active promoter-promoter, promoter-enhancer and enhancer-enhancer associations identified by EpiTensor are highly concordant with those detected by Hi-C, ChIA-PET and eQTL analyses at 200 bp resolution. Moreover, EpiTensor has identified a set of interaction hotspots, characterized by higher chromatin and transcriptional activity as well as enriched TF and ncRNA binding across diverse cell types, which may be critical for stabilizing the local 3D interactions.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.
authors.forename: Kai
authors.identifier: http://orcid.org/0000-0003-3454-7357
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.
authors.forename: Mengchi
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.
authors.forename: David
authors.initials: D
authors.lastname: Medovoy
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Whitaker
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Ding
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.
authors.forename: Nan
authors.identifier: http://orcid.org/0000-0001-7826-4688
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0359, USA.|Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093-0359, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D002874:Chromosome Mapping; D057890:Epigenomics; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin