Dynamic Regulation of Nucleosome Positioning in the Human Genome

Dustin E. Schones; Kairong Cui; Suresh Cuddapah; Tae Young Roh; Artem Barski; Zhibin Wang; Gang Wei; Keji Zhao

doi:10.1016/j.cell.2008.02.022

Dynamic Regulation of Nucleosome Positioning in the Human Genome

Dustin E. Schones, Kairong Cui, Suresh Cuddapah, Tae Young Roh, Artem Barski, Zhibin Wang, Gang Wei, Keji Zhao

Life Sciences

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

1067 Scopus citations

Abstract

The positioning of nucleosomes with respect to DNA plays an important role in regulating transcription. However, nucleosome mapping has been performed for only limited genomic regions in humans. We have generated genome-wide maps of nucleosome positions in both resting and activated human CD4⁺ T cells by direct sequencing of nucleosome ends using the Solexa high-throughput sequencing technique. We find that nucleosome phasing relative to the transcription start sites is directly correlated to RNA polymerase II (Pol II) binding. Furthermore, the first nucleosome downstream of a start site exhibits differential positioning in active and silent genes. TCR signaling induces extensive nucleosome reorganization in promoters and enhancers to allow transcriptional activation or repression. Our results suggest that H2A.Z-containing and modified nucleosomes are preferentially lost from the -1 nucleosome position. Our data provide a comprehensive view of the nucleosome landscape and its dynamic regulation in the human genome.

Original language	English
Pages (from-to)	887-898
Number of pages	12
Journal	Cell
Volume	132
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2008.02.022
State	Published - 7 Mar 2008

Keywords

DNA
SIGNALING

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10.1016/j.cell.2008.02.022

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@article{8712b1e560fc4b5a85391099123f4510,

title = "Dynamic Regulation of Nucleosome Positioning in the Human Genome",

abstract = "The positioning of nucleosomes with respect to DNA plays an important role in regulating transcription. However, nucleosome mapping has been performed for only limited genomic regions in humans. We have generated genome-wide maps of nucleosome positions in both resting and activated human CD4+ T cells by direct sequencing of nucleosome ends using the Solexa high-throughput sequencing technique. We find that nucleosome phasing relative to the transcription start sites is directly correlated to RNA polymerase II (Pol II) binding. Furthermore, the first nucleosome downstream of a start site exhibits differential positioning in active and silent genes. TCR signaling induces extensive nucleosome reorganization in promoters and enhancers to allow transcriptional activation or repression. Our results suggest that H2A.Z-containing and modified nucleosomes are preferentially lost from the -1 nucleosome position. Our data provide a comprehensive view of the nucleosome landscape and its dynamic regulation in the human genome.",

keywords = "DNA, SIGNALING",

author = "Schones, {Dustin E.} and Kairong Cui and Suresh Cuddapah and Roh, {Tae Young} and Artem Barski and Zhibin Wang and Gang Wei and Keji Zhao",

note = "Funding Information: The gene expression analysis using the Affymetrix microarrays was performed by the Gene Expression Core Facility of NHLBI. This work was supported by the Intramural Research Program of the NIH, National Heart, Lung and Blood Institute. We thank Weiqun Peng, Chongzhi Zang, and Raja Jothi for helpful comments and discussions. ",

year = "2008",

month = mar,

day = "7",

doi = "10.1016/j.cell.2008.02.022",

language = "English",

volume = "132",

pages = "887--898",

journal = "Cell",

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AU - Schones, Dustin E.

AU - Cui, Kairong

AU - Cuddapah, Suresh

AU - Roh, Tae Young

AU - Barski, Artem

AU - Wang, Zhibin

AU - Wei, Gang

AU - Zhao, Keji

N1 - Funding Information: The gene expression analysis using the Affymetrix microarrays was performed by the Gene Expression Core Facility of NHLBI. This work was supported by the Intramural Research Program of the NIH, National Heart, Lung and Blood Institute. We thank Weiqun Peng, Chongzhi Zang, and Raja Jothi for helpful comments and discussions.

PY - 2008/3/7

Y1 - 2008/3/7

N2 - The positioning of nucleosomes with respect to DNA plays an important role in regulating transcription. However, nucleosome mapping has been performed for only limited genomic regions in humans. We have generated genome-wide maps of nucleosome positions in both resting and activated human CD4+ T cells by direct sequencing of nucleosome ends using the Solexa high-throughput sequencing technique. We find that nucleosome phasing relative to the transcription start sites is directly correlated to RNA polymerase II (Pol II) binding. Furthermore, the first nucleosome downstream of a start site exhibits differential positioning in active and silent genes. TCR signaling induces extensive nucleosome reorganization in promoters and enhancers to allow transcriptional activation or repression. Our results suggest that H2A.Z-containing and modified nucleosomes are preferentially lost from the -1 nucleosome position. Our data provide a comprehensive view of the nucleosome landscape and its dynamic regulation in the human genome.

AB - The positioning of nucleosomes with respect to DNA plays an important role in regulating transcription. However, nucleosome mapping has been performed for only limited genomic regions in humans. We have generated genome-wide maps of nucleosome positions in both resting and activated human CD4+ T cells by direct sequencing of nucleosome ends using the Solexa high-throughput sequencing technique. We find that nucleosome phasing relative to the transcription start sites is directly correlated to RNA polymerase II (Pol II) binding. Furthermore, the first nucleosome downstream of a start site exhibits differential positioning in active and silent genes. TCR signaling induces extensive nucleosome reorganization in promoters and enhancers to allow transcriptional activation or repression. Our results suggest that H2A.Z-containing and modified nucleosomes are preferentially lost from the -1 nucleosome position. Our data provide a comprehensive view of the nucleosome landscape and its dynamic regulation in the human genome.

KW - DNA

KW - SIGNALING

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DO - 10.1016/j.cell.2008.02.022

M3 - Article

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AN - SCOPUS:39749145198

SN - 0092-8674

VL - 132

SP - 887

EP - 898

JO - Cell

JF - Cell

IS - 5

ER -

Dynamic Regulation of Nucleosome Positioning in the Human Genome

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Keywords

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