title: A Compendium of Chromatin Contact Maps Reveals Spatially Active Regions in the Human Genome.
abstract: The three-dimensional configuration of DNA is integral to all nuclear processes in eukaryotes, yet our knowledge of the chromosome architecture is still limited. Genome-wide chromosome conformation capture studies have uncovered features of chromatin organization in cultured cells, but genome architecture in human tissues has yet to be explored. Here, we report the most comprehensive survey to date of chromatin organization in human tissues. Through integrative analysis of chromatin contact maps in 21 primary human tissues and cell types, we find topologically associating domains highly conserved in different tissues. We also discover genomic regions that exhibit unusually high levels of local chromatin interactions. These frequently interacting regions (FIREs) are enriched for super-enhancers and are near tissue-specifically expressed genes. They display strong tissue-specificity in local chromatin interactions. Additionally, FIRE formation is partially dependent on CTCF and the Cohesin complex. We further show that FIREs can help annotate the function of non-coding sequence variants.
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; UCSD Biomedical Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Schmitt
authors.affiliation: Division of Biostatistics, Department of Population Health, New York University School of Medicine, 650 First Avenue, New York, NY 10016, USA. Electronic address: hum@ccf.org.
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
authors.forename: Inkyung
authors.initials: I
authors.lastname: Jung
authors.affiliation: Departments of Genetics, Biostatistics, and Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA; Quantitative Life Sciences Initiative, University of Nebraska, Lincoln, NE 68583, USA; Department of Statistics, University of Nebraska, Lincoln, NE 68583, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; USCD Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Yunjiang
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Tan
authors.affiliation: Departments of Genetics, Biostatistics, and Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Cardiology, Department of Medicine, University of Washington, 850 Republican Street, Seattle, WA 98108, USA.
authors.forename: Shin
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Surgery, Washington University School of Medicine, 660 S Euclid Ave., Campus Box 8109, St. Louis, MO 63110, USA.
authors.forename: Yiing
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Krembil Research Institute University Health Network, The Hospital for Sick Children, The University of Toronto, Krembil Discovery Tower, 60 Leonard Ave. 8KD-412, Toronto, ON M5T 2S8, Canada.
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Barr
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, Moores Cancer Center and Institute of Genome Medicine, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: biren@ucsd.edu.
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
mesh_terms: D000328:Adult; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D017124:Conserved Sequence; D004194:Disease / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D038101:Insulator Elements / Q000235:genetics; D051379:Mice; D009690:Nucleic Acid Conformation; D009928:Organ Specificity; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins