Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing

Diana A. Stavreva; Antoine Coulon; Songjoon Baek; Myong Hee Sung; Sam John; Lenka Stixova; Martina Tesikova; Ofir Hakim; Tina Miranda; Mary Hawkins; John A. Stamatoyannopoulos; Carson C. Chow; Gordon L. Hager

doi:10.1101/gr.184168.114

Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing

Diana A. Stavreva, Antoine Coulon, Songjoon Baek, Myong Hee Sung, Sam John, Lenka Stixova, Martina Tesikova, Ofir Hakim, Tina Miranda, Mary Hawkins, John A. Stamatoyannopoulos, Carson C. Chow, Gordon L. Hager

The Mina and Everard Goodman Faculty of Life Sciences

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

72 Scopus citations

Abstract

Although physiological steroid levels are often pulsatile (ultradian), the genomic effects of this pulsatility are poorly understood. By utilizing glucocorticoid receptor (GR) signaling as a model system, we uncovered striking spatiotemporal relationships between receptor loading, lifetimes of the DNase I hypersensitivity sites (DHSs), long-range interactions, and gene regulation. We found that hormone-induced DHSs were enriched within ±50 kb of GR-responsive genes and displayed a broad spectrum of lifetimes upon hormone withdrawal. These lifetimes dictate the strength of the DHS interactions with gene targets and contribute to gene regulation from a distance. Our results demonstrate that pulsatile and constant hormone stimulations induce unique, treatment-specific patterns of gene and regulatory element activation. These modes of activation have implications for corticosteroid function in vivo and for steroid therapies in various clinical settings.

Original language	English
Pages (from-to)	845-857
Number of pages	13
Journal	Genome Research
Volume	25
Issue number	6
DOIs	https://doi.org/10.1101/gr.184168.114
State	Published - 1 Jun 2015

Bibliographical note

Publisher Copyright:
© 2015 Stavreva et al.

Funding

Funders	Funder number
National Cancer Institute	ZICBC011574
National Institute of Diabetes and Digestive and Kidney Diseases	ZIADK075069

Access to Document

10.1101/gr.184168.114

Cite this

@article{3643ff55051645d39490cd5a079b16fc,

title = "Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing",

abstract = "Although physiological steroid levels are often pulsatile (ultradian), the genomic effects of this pulsatility are poorly understood. By utilizing glucocorticoid receptor (GR) signaling as a model system, we uncovered striking spatiotemporal relationships between receptor loading, lifetimes of the DNase I hypersensitivity sites (DHSs), long-range interactions, and gene regulation. We found that hormone-induced DHSs were enriched within ±50 kb of GR-responsive genes and displayed a broad spectrum of lifetimes upon hormone withdrawal. These lifetimes dictate the strength of the DHS interactions with gene targets and contribute to gene regulation from a distance. Our results demonstrate that pulsatile and constant hormone stimulations induce unique, treatment-specific patterns of gene and regulatory element activation. These modes of activation have implications for corticosteroid function in vivo and for steroid therapies in various clinical settings.",

author = "Stavreva, {Diana A.} and Antoine Coulon and Songjoon Baek and Sung, {Myong Hee} and Sam John and Lenka Stixova and Martina Tesikova and Ofir Hakim and Tina Miranda and Mary Hawkins and Stamatoyannopoulos, {John A.} and Chow, {Carson C.} and Hager, {Gordon L.}",

note = "Publisher Copyright: {\textcopyright} 2015 Stavreva et al.",

year = "2015",

month = jun,

day = "1",

doi = "10.1101/gr.184168.114",

language = "אנגלית",

volume = "25",

pages = "845--857",

journal = "Genome Research",

issn = "1088-9051",

publisher = "Cold Spring Harbor Laboratory Press",

number = "6",

}

TY - JOUR

T1 - Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing

AU - Stavreva, Diana A.

AU - Coulon, Antoine

AU - Baek, Songjoon

AU - Sung, Myong Hee

AU - John, Sam

AU - Stixova, Lenka

AU - Tesikova, Martina

AU - Hakim, Ofir

AU - Miranda, Tina

AU - Hawkins, Mary

AU - Stamatoyannopoulos, John A.

AU - Chow, Carson C.

AU - Hager, Gordon L.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Although physiological steroid levels are often pulsatile (ultradian), the genomic effects of this pulsatility are poorly understood. By utilizing glucocorticoid receptor (GR) signaling as a model system, we uncovered striking spatiotemporal relationships between receptor loading, lifetimes of the DNase I hypersensitivity sites (DHSs), long-range interactions, and gene regulation. We found that hormone-induced DHSs were enriched within ±50 kb of GR-responsive genes and displayed a broad spectrum of lifetimes upon hormone withdrawal. These lifetimes dictate the strength of the DHS interactions with gene targets and contribute to gene regulation from a distance. Our results demonstrate that pulsatile and constant hormone stimulations induce unique, treatment-specific patterns of gene and regulatory element activation. These modes of activation have implications for corticosteroid function in vivo and for steroid therapies in various clinical settings.

AB - Although physiological steroid levels are often pulsatile (ultradian), the genomic effects of this pulsatility are poorly understood. By utilizing glucocorticoid receptor (GR) signaling as a model system, we uncovered striking spatiotemporal relationships between receptor loading, lifetimes of the DNase I hypersensitivity sites (DHSs), long-range interactions, and gene regulation. We found that hormone-induced DHSs were enriched within ±50 kb of GR-responsive genes and displayed a broad spectrum of lifetimes upon hormone withdrawal. These lifetimes dictate the strength of the DHS interactions with gene targets and contribute to gene regulation from a distance. Our results demonstrate that pulsatile and constant hormone stimulations induce unique, treatment-specific patterns of gene and regulatory element activation. These modes of activation have implications for corticosteroid function in vivo and for steroid therapies in various clinical settings.

UR - http://www.scopus.com/inward/record.url?scp=84931829469&partnerID=8YFLogxK

U2 - 10.1101/gr.184168.114

DO - 10.1101/gr.184168.114

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 25677181

AN - SCOPUS:84931829469

SN - 1088-9051

VL - 25

SP - 845

EP - 857

JO - Genome Research

JF - Genome Research

IS - 6

ER -

Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing

Abstract

Bibliographical note

Funding

Access to Document

Other files and links

Fingerprint

Cite this