Subnuclear trafficking and gene targeting by steroid receptors

Akhilesh K. Nagaich, Geetha V. Rayasam, Elisabeth D. Martinez, Matthias Becker, Yi Qiu, Thomas A. Johnson, Cem Elbi, Terace M. Fletcher, Sam John, Gordon L. Hager

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Through the use of novel imaging techniques, we have observed direct steroid receptor binding to a tandem array of a hormone-responsive promoter in living cells. We found that the glucocorticoid receptor (GR) exchanges rapidly with regulatory elements in the continued presence of ligand. We have also reconstituted a GR-dependent nucleoprotein transition with chromatin assembled on promoter DNA, and we discovered that GR is actively displaced from the chromatin template during the chromatin remodeling process. Using high-intensity UV laser crosslinking, we have observed highly periodic interactions of GR with promoter chromatin. These periodic binding events are dependent on GR-directed hSWI/SNF remodeling of the template and require the presence of ATP. Both the in vitro and in vivo results are consistent with a dynamic model ("hit-and-run") in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, and is simultaneously lost from the template. We also find that receptor mobility in the nucleoplasm is strongly enhanced by molecular chaperones. These observations indicate that multiple mechanisms are involved in transient receptor interactions with nucleoplasmic targets.

Original languageEnglish (US)
Pages (from-to)213-220
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume1024
DOIs
StatePublished - 2004

Fingerprint

Gene Targeting
Steroid Receptors
Glucocorticoid Receptors
Genes
Chromatin
Ligands
Molecular Chaperones
Nucleoproteins
Chromatin Assembly and Disassembly
Crosslinking
Template
Gene
Steroids
Dynamic models
Lasers
Adenosine Triphosphate
Chemical activation
Cells
Hormones
Imaging techniques

Keywords

  • Chaperone
  • Chromatin
  • FRAP
  • Glucocorticoid receptor
  • Laser crosslinking
  • Nuclear receptor
  • Progesterone receptor
  • Protein dynamics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nagaich, A. K., Rayasam, G. V., Martinez, E. D., Becker, M., Qiu, Y., Johnson, T. A., ... Hager, G. L. (2004). Subnuclear trafficking and gene targeting by steroid receptors. Annals of the New York Academy of Sciences, 1024, 213-220. https://doi.org/10.1196/annals.1321.002

Subnuclear trafficking and gene targeting by steroid receptors. / Nagaich, Akhilesh K.; Rayasam, Geetha V.; Martinez, Elisabeth D.; Becker, Matthias; Qiu, Yi; Johnson, Thomas A.; Elbi, Cem; Fletcher, Terace M.; John, Sam; Hager, Gordon L.

In: Annals of the New York Academy of Sciences, Vol. 1024, 2004, p. 213-220.

Research output: Contribution to journalArticle

Nagaich, AK, Rayasam, GV, Martinez, ED, Becker, M, Qiu, Y, Johnson, TA, Elbi, C, Fletcher, TM, John, S & Hager, GL 2004, 'Subnuclear trafficking and gene targeting by steroid receptors', Annals of the New York Academy of Sciences, vol. 1024, pp. 213-220. https://doi.org/10.1196/annals.1321.002
Nagaich, Akhilesh K. ; Rayasam, Geetha V. ; Martinez, Elisabeth D. ; Becker, Matthias ; Qiu, Yi ; Johnson, Thomas A. ; Elbi, Cem ; Fletcher, Terace M. ; John, Sam ; Hager, Gordon L. / Subnuclear trafficking and gene targeting by steroid receptors. In: Annals of the New York Academy of Sciences. 2004 ; Vol. 1024. pp. 213-220.
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