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

doi:10.1038/nmeth.3205

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 journal › Article › peer-review

149 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 language	English (US)
Pages (from-to)	71-78
Number of pages	8
Journal	Nature Methods
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/nmeth.3205
State	Published - Jan 1 2014

ASJC Scopus subject areas

Molecular Biology
Biochemistry
Biotechnology
Cell Biology

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title = "Fine-scale chromatin interaction maps reveal the cis-regulatory landscape of human lincRNA genes",

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.",

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

note = "Funding Information: We thank S. Fields and M. Groudine for critical reading of the manuscript. This work was supported by US National Institutes of Health grants R01 GM098039 (C.A.B.), GM046883 (C.M.D.) and R01 U41HG007000 (W.S.N.).",

year = "2014",

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doi = "10.1038/nmeth.3205",

language = "English (US)",

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AU - Ma, Wenxiu

AU - Ay, Ferhat

AU - Lee, Choli

AU - Gulsoy, Gunhan

AU - Deng, Xinxian

AU - Cook, Savannah

AU - Hesson, Jennifer

AU - Cavanaugh, Christopher

AU - Ware, Carol B.

AU - Krumm, Anton

AU - Shendure, Jay

AU - Blau, Carl Anthony

AU - Disteche, Christine M.

AU - Noble, William S.

AU - Duan, Zhijun

N1 - Funding Information: We thank S. Fields and M. Groudine for critical reading of the manuscript. This work was supported by US National Institutes of Health grants R01 GM098039 (C.A.B.), GM046883 (C.M.D.) and R01 U41HG007000 (W.S.N.).

PY - 2014/1/1

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N2 - 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.

AB - 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.

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

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