Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data

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Abstract

Analysis of Hi-C data has shown that the genome can be divided into two compartments called A/B compartments. These compartments are cell-type specific and are associated with open and closed chromatin. We show that A/B compartments can reliably be estimated using epigenetic data from several different platforms: the Illumina 450 k DNA methylation microarray, DNase hypersensitivity sequencing, single-cell ATAC sequencing and single-cell whole-genome bisulfite sequencing. We do this by exploiting that the structure of long-range correlations differs between open and closed compartments. This work makes A/B compartment assignment readily available in a wide variety of cell types, including many human cancers.

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The online version of this article (doi:10.1186/s13059-015-0741-y) contains supplementary material, which is available to authorized users.

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High density DNA methylation array with single CpG site resolution.

Marina Bibikova, Bret Barnes, Chan Tsan … (2011)

We have developed a new generation of genome-wide DNA methylation BeadChip which allows high-throughput methylation profiling of the human genome. The new high density BeadChip can assay over 480K CpG sites and analyze twelve samples in parallel. The innovative content includes coverage of 99% of RefSeq genes with multiple probes per gene, 96% of CpG islands from the UCSC database, CpG island shores and additional content selected from whole-genome bisulfite sequencing data and input from DNA methylation experts. The well-characterized Infinium® Assay is used for analysis of CpG methylation using bisulfite-converted genomic DNA. We applied this technology to analyze DNA methylation in normal and tumor DNA samples and compared results with whole-genome bisulfite sequencing (WGBS) data obtained for the same samples. Highly comparable DNA methylation profiles were generated by the array and sequencing methods (average R2 of 0.95). The ability to determine genome-wide methylation patterns will rapidly advance methylation research. Copyright © 2011 Elsevier Inc. All rights reserved.

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High-resolution mapping and characterization of open chromatin across the genome.

Alan Boyle, Sean Davis, Hennady Shulha … (2008)

Mapping DNase I hypersensitive (HS) sites is an accurate method of identifying the location of genetic regulatory elements, including promoters, enhancers, silencers, insulators, and locus control regions. We employed high-throughput sequencing and whole-genome tiled array strategies to identify DNase I HS sites within human primary CD4+ T cells. Combining these two technologies, we have created a comprehensive and accurate genome-wide open chromatin map. Surprisingly, only 16%-21% of the identified 94,925 DNase I HS sites are found in promoters or first exons of known genes, but nearly half of the most open sites are in these regions. In conjunction with expression, motif, and chromatin immunoprecipitation data, we find evidence of cell-type-specific characteristics, including the ability to identify transcription start sites and locations of different chromatin marks utilized in these cells. In addition, and unexpectedly, our analyses have uncovered detailed features of nucleosome structure.

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Organization of the mitotic chromosome.

Natalia Naumova, Maxim Imakaev, Geoffrey Fudenberg … (2013)

Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell type-specific organization described previously for nonsynchronous cells is restricted to interphase. In metaphase, we identified a homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we found that metaphase Hi-C data are inconsistent with classic hierarchical models and are instead best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.

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Author and article information

Contributors

Jean-Philippe Fortin: fortin@jhsph.edu

Kasper D. Hansen: khansen@jhsph.edu

Journal

Journal ID (nlm-ta): Genome Biol

Journal ID (iso-abbrev): Genome Biol

Title: Genome Biology

Publisher: BioMed Central (London )

ISSN (Print): 1474-7596

ISSN (Electronic): 1474-760X

Publication date (Electronic): 28 August 2015

Publication date PMC-release: 28 August 2015

Publication date (Print): 2015

Volume: 16

Issue: 1

Electronic Location Identifier: 180

Affiliations

[ ]Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Road, Baltimore, 21205 MD USA

[ ]McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, 1900 East Monument Street, Baltimore, 21205 MD USA

Article

Publisher ID: 741

DOI: 10.1186/s13059-015-0741-y

PMC ID: 4574526

PubMed ID: 26316348

SO-VID: 4e2cf6b5-4372-40ec-aaa9-ae588c5a66a1

License:

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 22 April 2015

Date accepted : 31 July 2015

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ScienceOpen disciplines: Genetics

Keywords: methylation,chromatin,epigenetics,chromosome configuration capture,single-cell,hi-c,dnase sequencing

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ScienceOpen disciplines: Genetics

Keywords: methylation, chromatin, epigenetics, chromosome configuration capture, single-cell, hi-c, dnase sequencing

Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data

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Abstract

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Most cited references 14

High density DNA methylation array with single CpG site resolution.

High-resolution mapping and characterization of open chromatin across the genome.

Organization of the mitotic chromosome.

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