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Nat Methods. 2015 Jan;12(1):71-8. doi: 10.1038/nmeth.3205. Epub 2014 Dec 1.

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

Author information

1
Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
2
Department of Pathology, University of Washington, Seattle, Washington, USA.
3
1] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, USA. [2] Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
4
Department of Radiation Oncology, University of Washington, Seattle, Washington, USA.
5
1] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, USA. [2] Division of Hematology, University of Washington, Seattle, Washington, USA.

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.

PMID:
25437436
PMCID:
PMC4281301
DOI:
10.1038/nmeth.3205
[Indexed for MEDLINE]
Free PMC Article
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