Impact of chromatin structure on PR signaling: transition from local to global analysis

Lars Grøntved, Gordon L Hager

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The progesterone receptor (PR) interacts with chromatin in a highly dynamic manner that requires ongoing chromatin remodeling, interaction with chaparones and activity of the proteasome. Here we discuss dynamic interaction of steroid receptor with chromatin, with special attention not only to PR but also to the glucocorticoid receptor (GR), as these receptors share many similarities regarding interaction with, and remodeling of, chromatin. Both receptors can bind nucleosomal DNA and have accordingly been described as pioneering factors. However recent genomic approaches (ChIP-seq and DHS-seq) show that a large fraction of receptor binding events occur at pre-accessible chromatin. Thus factors which generate and maintain accessible chromatin during development, and in fully differentiated tissue, contribute a major fraction of receptor tissue specificity. In addition, chromosome conformation capture techniques suggest that steroid receptors preferentially sequester within distinct nuclear hubs. We will integrate dynamic studies from single cells and genomic studies from cell populations, and discuss how genomic approaches have reshaped our current understanding of mechanisms that control steroid receptor interaction with chromatin.

Original languageEnglish
JournalMolecular and Cellular Endocrinology
Volume357
Issue number1-2
Pages (from-to)30-36
ISSN0303-7207
DOIs
Publication statusPublished - 2012
Externally publishedYes

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Progesterone Receptors
Chromatin
Steroid Receptors
Chromatin Assembly and Disassembly
Metagenomics
Organ Specificity
Glucocorticoid Receptors
Proteasome Endopeptidase Complex
Tissue
Chromosomes
Conformations
DNA
Cells

Keywords

  • Animals
  • Chromatin
  • Gene Expression Regulation
  • Humans
  • Receptors, Progesterone
  • Receptors, Steroid
  • Signal Transduction

Cite this

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title = "Impact of chromatin structure on PR signaling: transition from local to global analysis",
abstract = "The progesterone receptor (PR) interacts with chromatin in a highly dynamic manner that requires ongoing chromatin remodeling, interaction with chaparones and activity of the proteasome. Here we discuss dynamic interaction of steroid receptor with chromatin, with special attention not only to PR but also to the glucocorticoid receptor (GR), as these receptors share many similarities regarding interaction with, and remodeling of, chromatin. Both receptors can bind nucleosomal DNA and have accordingly been described as pioneering factors. However recent genomic approaches (ChIP-seq and DHS-seq) show that a large fraction of receptor binding events occur at pre-accessible chromatin. Thus factors which generate and maintain accessible chromatin during development, and in fully differentiated tissue, contribute a major fraction of receptor tissue specificity. In addition, chromosome conformation capture techniques suggest that steroid receptors preferentially sequester within distinct nuclear hubs. We will integrate dynamic studies from single cells and genomic studies from cell populations, and discuss how genomic approaches have reshaped our current understanding of mechanisms that control steroid receptor interaction with chromatin.",
keywords = "Animals, Chromatin, Gene Expression Regulation, Humans, Receptors, Progesterone, Receptors, Steroid, Signal Transduction",
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Impact of chromatin structure on PR signaling : transition from local to global analysis. / Grøntved, Lars; Hager, Gordon L.

In: Molecular and Cellular Endocrinology, Vol. 357, No. 1-2, 2012, p. 30-36.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Impact of chromatin structure on PR signaling

T2 - transition from local to global analysis

AU - Grøntved, Lars

AU - Hager, Gordon L

N1 - Published by Elsevier Ireland Ltd.

PY - 2012

Y1 - 2012

N2 - The progesterone receptor (PR) interacts with chromatin in a highly dynamic manner that requires ongoing chromatin remodeling, interaction with chaparones and activity of the proteasome. Here we discuss dynamic interaction of steroid receptor with chromatin, with special attention not only to PR but also to the glucocorticoid receptor (GR), as these receptors share many similarities regarding interaction with, and remodeling of, chromatin. Both receptors can bind nucleosomal DNA and have accordingly been described as pioneering factors. However recent genomic approaches (ChIP-seq and DHS-seq) show that a large fraction of receptor binding events occur at pre-accessible chromatin. Thus factors which generate and maintain accessible chromatin during development, and in fully differentiated tissue, contribute a major fraction of receptor tissue specificity. In addition, chromosome conformation capture techniques suggest that steroid receptors preferentially sequester within distinct nuclear hubs. We will integrate dynamic studies from single cells and genomic studies from cell populations, and discuss how genomic approaches have reshaped our current understanding of mechanisms that control steroid receptor interaction with chromatin.

AB - The progesterone receptor (PR) interacts with chromatin in a highly dynamic manner that requires ongoing chromatin remodeling, interaction with chaparones and activity of the proteasome. Here we discuss dynamic interaction of steroid receptor with chromatin, with special attention not only to PR but also to the glucocorticoid receptor (GR), as these receptors share many similarities regarding interaction with, and remodeling of, chromatin. Both receptors can bind nucleosomal DNA and have accordingly been described as pioneering factors. However recent genomic approaches (ChIP-seq and DHS-seq) show that a large fraction of receptor binding events occur at pre-accessible chromatin. Thus factors which generate and maintain accessible chromatin during development, and in fully differentiated tissue, contribute a major fraction of receptor tissue specificity. In addition, chromosome conformation capture techniques suggest that steroid receptors preferentially sequester within distinct nuclear hubs. We will integrate dynamic studies from single cells and genomic studies from cell populations, and discuss how genomic approaches have reshaped our current understanding of mechanisms that control steroid receptor interaction with chromatin.

KW - Animals

KW - Chromatin

KW - Gene Expression Regulation

KW - Humans

KW - Receptors, Progesterone

KW - Receptors, Steroid

KW - Signal Transduction

U2 - 10.1016/j.mce.2011.09.006

DO - 10.1016/j.mce.2011.09.006

M3 - Journal article

C2 - 21958695

VL - 357

SP - 30

EP - 36

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

IS - 1-2

ER -