Localization of the glucocorticoid receptor in discrete clusters in the cell nucleus.

Abstract:

:The cell nucleus is highly organized. Many nuclear functions are localized in discrete domains, suggesting that compartmentalization is an important aspect of the regulation and coordination of nuclear functions. We investigated the subnuclear distribution of the glucocorticoid receptor, a hormone-dependent transcription factor. By immunofluorescent labeling and confocal microscopy we found that after stimulation with the agonist dexamethasone the glucocorticoid receptor is concentrated in 1,000-2,000 clusters in the nucleoplasm. This distribution was observed in several cell types and with three different antibodies against the glucocorticoid receptor. A similar subnuclear distribution of glucocorticoid receptors was found after treatment of cells with the antagonist RU486, suggesting that the association of the glucocorticoid receptor in clusters does not require transformation of the receptor to a state that is able to activate transcription. By dual labeling we found that most dexamethasone-induced receptor clusters do not colocalize with sites of pre-mRNA synthesis. We also show that RNA polymerase II is localized in a large number of clusters in the nucleus. Glucocorticoid receptor clusters did not significantly colocalize with these RNA polymerase II clusters or with domains containing the splicing factor SC-35. Taken together, these results suggest that most clustered glucocorticoid receptor molecules are not directly involved in activation of transcription.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

van Steensel B,Brink M,van der Meulen K,van Binnendijk EP,Wansink DG,de Jong L,de Kloet ER,van Driel R

subject

Has Abstract

pub_date

1995-09-01 00:00:00

pages

3003-11

eissn

0021-9533

issn

1477-9137

journal_volume

108 ( Pt 9)

pub_type

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