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Subnuclear Trafficking and Gene Targeting by Steroid Receptors
Author(s) -
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.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1321.002
Subject(s) - chromatin , chromatin remodeling , glucocorticoid receptor , microbiology and biotechnology , receptor , nucleoplasm , nuclear receptor , biology , chemistry , dna , gene , transcription factor , genetics , nucleolus , nucleus
A bstract : 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.