Transcriptional regulation by members of the nuclear hormone receptor superfamily is a modular process requiring the mediation of distinct subclasses of coregulators. These subclasses include members of the steroid receptor coactivator-1 (SRC-1) coactivator family, p300/CBP and their associated proteins, such as p300/CBP-associated factor, human homologs of SWI/SNF proteins such as BRG-1, and the less well-characterized E3 ubiquitin- protein ligases E6 papillomavirus protein-associated protein and receptor- potentiating factor-1. Because functional studies indicate that these coregulators may form higher order complexes, we analyzed stead-state complexes of different coregulator subclasses in vivo. T47D and HeLa cell lysates were subjected to biochemical fractionation and screened by immunoblotting using coregulator-specific antibodies. We show that different subclasses of nuclear receptor coregulators exhibit distinct fractionation profiles. Furthermore, evidence is provided that SRC-1 family members may exist in vivo in heteromultimeric forms with each other. In addition, we demonstrate that liganded PR is present in stable complexes containing SRC-1 and transcription intermediary factor 2 (TIF2) in vivo. Our results suggest that the assembly of large, modular transcriptional complexes by recruitment of distinct subclasses of preformed coregulator subcomplexes may be involved in transcriptional regulation by activated nuclear receptors.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Sep 29 1998|
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