Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes

Wenxiu Ma, Ferhat Ay, Choli Lee, Gunhan Gulsoy, Xinxian Deng, Savannah Cook, Jennifer Hesson, Christopher Cavanaugh, Carol B. Ware, Anton Krumm, Jay Shendure, Carl Anthony Blau, Christine M. Disteche, William S. Noble*, Zhijun Duan

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    115 Scopus citations

    Abstract

    High-throughput methods based on chromosome conformation capture have greatly advanced our understanding of the three-dimensional (3D) organization of genomes but are limited in resolution by their reliance on restriction enzymes. Here we describe a method called DNase Hi-C for comprehensively mapping global chromatin contacts. DNase Hi-C uses DNase I for chromatin fragmentation, leading to greatly improved efficiency and resolution over that of Hi-C. Coupling this method with DNA-capture technology provides a high-throughput approach for targeted mapping of fine-scale chromatin architecture. We applied targeted DNase Hi-C to characterize the 3D organization of 998 large intergenic noncoding RNA (lincRNA) promoters in two human cell lines. Our results revealed that expression of lincRNAs is tightly controlled by complex mechanisms involving both super-enhancers and the Polycomb repressive complex. Our results provide the first glimpse of the cell type-specific 3D organization of lincRNA genes.

    Original languageEnglish (US)
    Pages (from-to)71-78
    Number of pages8
    JournalNature Methods
    Volume12
    Issue number1
    DOIs
    StatePublished - Jan 1 2014

    ASJC Scopus subject areas

    • Biotechnology
    • Biochemistry
    • Molecular Biology
    • Cell Biology

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