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

Anthony D. Schmitt, Ming Hu, Inkyung Jung, Zheng Xu, Yunjiang Qiu, Catherine L. Tan, Yun Li, Shin Lin, Yiing Lin, Cathy L. Barr, Bing Ren

Research output: Contribution to journalArticlepeer-review

372 Scopus citations

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.

Original languageEnglish
Pages (from-to)2042-2059
Number of pages18
JournalCell Reports
Volume17
Issue number8
DOIs
StatePublished - Nov 15 2016

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