Abstract
The assembly of transcriptional regulatory DNA sequences into chromatin plays a fundamental role in modulating gene expression1,2. The promoter of the mouse mammary-tumour virus (MMTV) is packaged into a regular array of nucleosomes when it becomes stably integrated into mammalian chromosomes, and has been used to investigate the relationship between chromatin architecture and transcriptional activation by the hormone-bound glucocorticoid and progesterone receptors3,4. In mammalian cells that express both of these receptors, the progesterone receptor activates transcription from transiently transfected MMTV DNA5,6 but not from organized chromatin templates7. Moreover, the activated progesterone receptor inhibits the chromatin remodelling and consequent transcriptional stimulation that is mediated by the glucocorticoid receptor. Here we investigate the mechanism of this inhibition by characterizing the interaction of the glucocorticoid receptor with transcriptional co-activator and chromatin remodelling protein complexes2,8. We show that when this receptor is prevented from interacting with the hBRG1/BAF chromatin remodelling complex, it can activate transcription from transiently transfected DNA but not from organized chromatin templates. Our results indicate that it may be possible to separate the transcriptional activation and chromatin remodelling activities of proteins that interact with hormone receptors.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Grunstein, M. Histone function in transcription. Annu. Rev. Cell. Biol. 6, 643–678 (1990).
Kingston, R. E., Bunker, C. A. & Imbalzano, A. N. Repression and activation by multiprotein complexes that alter chromatin structure. Genes Dev. 10, 905–920 (1996).
Richard-Foy, H. & Hager, G. L. Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter. EMBO J. 6, 2321–2328 (1987).
Archer, T. K.et al. Steroid hormone receptor status defines the MMTV promoter chromatin structure in vivo. J. Ster. Biochem. Mol. Biol. 53, 421–429 (1995).
Archer, T. K., Lefebvre, P., Wolford, R. G. & Hager, G. L. Transcription factor loading on the MMTV promoter: A bimodal mechanism for promoter activation. Science 255, 1573–1576 (1992).
Lee, H.-L. & Archer, T. K. Nucleosome-mediated disruption of transcription factor-chromatin initiation complexes at the mouse mammary tumor virus long terminal repeat in vivo. Mol. Cell. Biol. 14, 32–41 (1994).
Archer, T. K., Zaniewski, E., Moyer, M. L. & Nordeen, S. K. The differential capacity of glucocorticoids and progestins to alter chromatin structure and induce gene expression in human breast cancer cells. Mol. Endocr. 8, 1154–1162 (1994).
Glass, C. K., Rose, D. W. & Rosenfeld, M. G. Nuclear receptor coactivators. Curr. Opin. Cell Biol. 9, 222–232 (1997).
Mizutani, T., Bhakta, A., Kloosterboer, H. J. & Moudgil, V. K. Novel antiprogestins ORG 31806 and 31710: Interaction with mammalian progesterone receptor and DNA binding of antisteroid receptor complexes. J. Ster. Biochem. Mol. Biol. 42, 695–704 (1992).
Truss, M.et al. Hormone induces binding of receptors and transcription factors to a rearranged nucleosome on the MMTV promoter in vivo. EMBO J. 14, 1737–1751 (1995).
Yoshinaga, S. K., Peterson, C. L., Herskowitz, I. & Yamamoto, K. R. Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors. Science 258, 1598–1604 (1992).
Muchardt, C. & Yaniv, M. Ahuman homologue of Saccharomyces cerevisiae SNF2/SW12 and Drosophila brm genes potentiates transcriptional activation by the glucocorticoid receptor. EMBO J. 12, 4279–4290 (1993).
Östlund Farrangs, A.-K., Blomquist, P., Kwon, H. & Wrange, & Glucocorticoid receptor–glucocorticoid response element binding stimulates nucleosome disruption by the SWI/SNF complex. Mol. Cell. Biol. 17, 895–905 (1997).
Wang, W.et al. Diversity and specialization of mammalian SWI/SNF complexes. Genes Dev. 10, 2117–2130 (1996).
Horwitz, K. B.et al. Nuclear receptor coactivators and corepressors. Mol. Endocr. 10, 1167–1177 (1996).
Kamei, Y.et al. ACBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 85, 403–414 (1996).
Oñate, S. A., Tsai, S. Y., Tsai, M.-J. & O'Malley, B. W. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 270, 1354–1357 (1995).
Voegel, J. J.et al. TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors. EMBO J. 15, 3667–3675 (1996).
Ogryzko, V. V.et al. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87, 953–959 (1996).
Bannister, A. J. & Kouzarides, T. The CBP co-activator is a histone acetyltransferase. Nature 384, 641–643 (1996).
Bresnick, E. H.et al. Glucocorticoid receptor-dependent disruption of a specific nucleosome on the mouse mammary tumor virus promoter is prevented by sodium butyrate. Proc. Natl Acad. Sci. USA 87, 3977–3981 (1990).
McKnight, G. S., Hager, L. & Palmiter, R. D. Butyrate and related inhibitors of histone deacetylation block the induction of egg white genes by steroid hormones. Cell 22, 469–477 (1980).
Torchia, J.et al. The transcriptional co-activator p/CIP binds CBP and meditates nuclear-receptor function. Nature 387, 677–684 (1997).
Smith, C. L., Oñate, S. A., Tsai, M.-J. & O'Malley, B. W. REB binding protein acts synergistically with steroid receptor coactivator-1 to enhance steroid receptor-dependent transcription. Proc. Natl Acad. Sci. USA 93, 8884–8888 (1996).
Chakravarti, D.et al. Role of CBP/P300 in nuclear receptor signalling. Nature 383, 99–103 (1996).
Hong, H.et al. GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proc. Natl Acad. Sci. USA 93, 4948–4952 (1996).
Wu, C. Chromatin remodeling and the control of gene expression. J. Biol. Chem. 272, 28171–28174 (1997).
Dunaief, J. L.et al. The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell 79, 119–130 (1994).
Gametchu, B. & Harrison, R. W. Characterization of a monoclonal antibody ot the rat liver glucocorticoid receptor. Endocrinology 114, 274–279 (1984).
Estes, P. A.et al. Immunological analysis of progesterone receptors in human breast cancer. Biochemistry 26, 6250–6262 (1987).
Acknowledgements
We thank A. Imbalzano, G. Schnitzler and R. Kingston for hBRG1 antibody; B.Gametchu for the BUGR2 antibody; D. Edwards for the B-30 antibody; J. Torchia and M. Rosenfeld for NcoA1 and NcoA2 antibodies; W. Wang and G. Crabtree for BAFs 60a, 155 and 175 antibodies; S. Goff and B. Strober for hBRG1 plasmids; G. DiMattia and members of our laboratory for critically reading the manuscript; and D. Power for its preparation. This work was supported by grants to T.K.A. from the National Cancer Institute of Canada (NCIC) and the Medical Research Council (MRC) of Canada; T.K.A. is an NCIC Scientist and C.J.F. holds an MRC studentship award.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fryer, C., Archer, T. Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex. Nature 393, 88–91 (1998). https://doi.org/10.1038/30032
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/30032
This article is cited by
-
Natural compounds targeting nuclear receptors for effective cancer therapy
Cancer and Metastasis Reviews (2023)
-
Identification of a novel GR-ARID1a-P53BP1 protein complex involved in DNA damage repair and cell cycle regulation
Oncogene (2022)
-
SWI/SNF chromatin remodeler complex within the reward pathway is required for behavioral adaptations to stress
Nature Communications (2022)
-
Mechanisms behind context-dependent role of glucocorticoids in breast cancer progression
Cancer and Metastasis Reviews (2022)
-
Transglutaminase 2 mediates transcriptional regulation through BAF250a polyamination
Genes & Genomics (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.