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Cell Rep. 2016 Nov 15;17(8):2042-2059. doi: 10.1016/j.celrep.2016.10.061.

A Compendium of Chromatin Contact Maps Reveals Spatially Active Regions in the Human Genome.

Author information

1
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.
2
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.
3
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
4
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.
5
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.
6
Departments of Genetics, Biostatistics, and Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA.
7
Division of Cardiology, Department of Medicine, University of Washington, 850 Republican Street, Seattle, WA 98108, USA.
8
Department of Surgery, Washington University School of Medicine, 660 S Euclid Ave., Campus Box 8109, St. Louis, MO 63110, USA.
9
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.
10
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.

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.

PMID:
27851967
PMCID:
PMC5478386
DOI:
10.1016/j.celrep.2016.10.061
[Indexed for MEDLINE]
Free PMC Article

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