Recruitment of the SWI-SNF chromatin remodeling complex as a mechanism of gene activation by the glucocorticoid receptor tau1 activation domain.
The SWI-SNF complex has been shown to alter nucleosome conformation in an ATP-dependent manner, leading to increased accessibility of nucleosomal DNA to transcription factors. In this study, we show that the SWI-SNF complex can potentiate the activity of the glucocorticoid receptor (GR) through the N-terminal transactivation domain, tau1, in both yeast and mammalian cells. GR-tau1 can directly interact with purified SWI-SNF complex, and mutations in tau1 that affect the transactivation activity in vivo also directly affect tau1 interaction with SWI-SNF. Furthermore, the SWI-SNF complex can stimulate tau1-driven transcription from chromatin templates in vitro. Taken together, these results support a model in which the GR can directly recruit the SWI-SNF complex to target promoters during glucocorticoid-dependent gene activation. We also provide evidence that the SWI-SNF and SAGA complexes represent independent pathways of tau1-mediated activation but play overlapping roles that are able to compensate for one another under some conditions.
Wallberg
A E
AE
Karolinska Institute, Department of Biosciences, NOVUM, S-14157 Huddinge, Sweden. wallbea@rockvax.rockefeller.edu
Neely
K E
KE
Hassan
A H
AH
Gustafsson
J A
JA
Workman
J L
JL
Wright
A P
AP
D000595:Amino Acid Sequence; D002460:Cell Line; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D002843:Chromatin; D005656:Fungal Proteins; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors