Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays

Peter J. Sabo; Michael S. Kuehn; Robert Thurman; Brett E. Johnson; Ericka M. Johnson; Hua Cao; Man Yu; Elizabeth Rosenzweig; Jeff Goldy; Andrew Haydock; Molly Weaver; Anthony Shafer; Kristin Lee; Fidencio Neri; Richard Humbert; Michael A. Singer; Todd A. Richmond; Michael O. Dorschner; Michael McArthur; Michael Hawrylycz; Roland D. Green; Patrick A. Navas; William S. Noble; John A. Stamatoyannopoulos

doi:10.1038/nmeth890

Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays

Peter J. Sabo, Michael S. Kuehn, Robert Thurman, Brett E. Johnson, Ericka M. Johnson, Hua Cao, Man Yu, Elizabeth Rosenzweig, Jeff Goldy, Andrew Haydock, Molly Weaver, Anthony Shafer, Kristin Lee, Fidencio Neri, Richard Humbert, Michael A. Singer, Todd A. Richmond, Michael O. Dorschner, Michael McArthur, Michael HawrylyczRoland D. Green, Patrick A. Navas, William S. Noble, John A. Stamatoyannopoulos

Research output: Contribution to journal › Article › peer-review

271 Scopus citations

Abstract

Localized accessibility of critical DNA sequences to the regulatory machinery is a key requirement for regulation of human genes. Here we describe a high-resolution, genome-scale approach for quantifying chromatin accessibility by measuring DNase I sensitivity as a continuous function of genome position using tiling DNA microarrays (DNase-array). We demonstrate this approach across 1% (∼30 Mb) of the human genome, wherein we localized 2,690 classical DNase I hypersensitive sites with high sensitivity and specificity, and also mapped larger-scale patterns of chromatin architecture. DNase I hypersensitive sites exhibit marked aggregation around transcriptional start sites (TSSs), though the majority mark nonpromoter functional elements. We also developed a computational approach for visualizing higher-order features of chromatin structure. This revealed that human chromatin organization is dominated by large (100-500 kb) 'superclusters' of DNase I hypersensitive sites, which encompass both gene-rich and gene-poor regions. DNase-array is a powerful and straightforward approach for systematic exposition of the cis-regulatory architecture of complex genomes.

Original language	English (US)
Pages (from-to)	511-518
Number of pages	8
Journal	Nature Methods
Volume	3
Issue number	7
DOIs	https://doi.org/10.1038/nmeth890
State	Published - Jul 2006
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Biology
Cell Biology

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Sabo, P. J., Kuehn, M. S., Thurman, R., Johnson, B. E., Johnson, E. M., Cao, H., Yu, M., Rosenzweig, E., Goldy, J., Haydock, A., Weaver, M., Shafer, A., Lee, K., Neri, F., Humbert, R., Singer, M. A., Richmond, T. A., Dorschner, M. O., McArthur, M., ... Stamatoyannopoulos, J. A. (2006). Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays. Nature Methods, 3(7), 511-518. https://doi.org/10.1038/nmeth890

Sabo, PJ, Kuehn, MS, Thurman, R, Johnson, BE, Johnson, EM, Cao, H, Yu, M, Rosenzweig, E, Goldy, J, Haydock, A, Weaver, M, Shafer, A, Lee, K, Neri, F, Humbert, R, Singer, MA, Richmond, TA, Dorschner, MO, McArthur, M, Hawrylycz, M, Green, RD, Navas, PA, Noble, WS & Stamatoyannopoulos, JA 2006, 'Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays', Nature Methods, vol. 3, no. 7, pp. 511-518. https://doi.org/10.1038/nmeth890

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title = "Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays",

abstract = "Localized accessibility of critical DNA sequences to the regulatory machinery is a key requirement for regulation of human genes. Here we describe a high-resolution, genome-scale approach for quantifying chromatin accessibility by measuring DNase I sensitivity as a continuous function of genome position using tiling DNA microarrays (DNase-array). We demonstrate this approach across 1% (∼30 Mb) of the human genome, wherein we localized 2,690 classical DNase I hypersensitive sites with high sensitivity and specificity, and also mapped larger-scale patterns of chromatin architecture. DNase I hypersensitive sites exhibit marked aggregation around transcriptional start sites (TSSs), though the majority mark nonpromoter functional elements. We also developed a computational approach for visualizing higher-order features of chromatin structure. This revealed that human chromatin organization is dominated by large (100-500 kb) 'superclusters' of DNase I hypersensitive sites, which encompass both gene-rich and gene-poor regions. DNase-array is a powerful and straightforward approach for systematic exposition of the cis-regulatory architecture of complex genomes.",

author = "Sabo, {Peter J.} and Kuehn, {Michael S.} and Robert Thurman and Johnson, {Brett E.} and Johnson, {Ericka M.} and Hua Cao and Man Yu and Elizabeth Rosenzweig and Jeff Goldy and Andrew Haydock and Molly Weaver and Anthony Shafer and Kristin Lee and Fidencio Neri and Richard Humbert and Singer, {Michael A.} and Richmond, {Todd A.} and Dorschner, {Michael O.} and Michael McArthur and Michael Hawrylycz and Green, {Roland D.} and Navas, {Patrick A.} and Noble, {William S.} and Stamatoyannopoulos, {John A.}",

note = "Funding Information: This work was supported by grants from the US National Institute of General Medical Sciences and the National Human Genome Research Institute to J.A.S. and W.S.N.",

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doi = "10.1038/nmeth890",

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AU - Cao, Hua

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AU - Green, Roland D.

AU - Navas, Patrick A.

AU - Noble, William S.

AU - Stamatoyannopoulos, John A.

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N2 - Localized accessibility of critical DNA sequences to the regulatory machinery is a key requirement for regulation of human genes. Here we describe a high-resolution, genome-scale approach for quantifying chromatin accessibility by measuring DNase I sensitivity as a continuous function of genome position using tiling DNA microarrays (DNase-array). We demonstrate this approach across 1% (∼30 Mb) of the human genome, wherein we localized 2,690 classical DNase I hypersensitive sites with high sensitivity and specificity, and also mapped larger-scale patterns of chromatin architecture. DNase I hypersensitive sites exhibit marked aggregation around transcriptional start sites (TSSs), though the majority mark nonpromoter functional elements. We also developed a computational approach for visualizing higher-order features of chromatin structure. This revealed that human chromatin organization is dominated by large (100-500 kb) 'superclusters' of DNase I hypersensitive sites, which encompass both gene-rich and gene-poor regions. DNase-array is a powerful and straightforward approach for systematic exposition of the cis-regulatory architecture of complex genomes.

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Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays

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