Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex

The assembly of transcriptional regulatory DNA sequences into chromatin plays a fundamental role in modulating gene expression,. 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 receptors,. In mammalian cells that express both of these receptors, the progesterone receptor activates transcription from transiently transfected MMTV DNA, but not from organized chromatin templates. 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 complexes,. 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.

[1]  O. Wrange,et al.  Glucocorticoid receptor-glucocorticoid response element binding stimulates nucleosome disruption by the SWI/SNF complex , 1997, Molecular and cellular biology.

[2]  B. O’Malley,et al.  CREB binding protein acts synergistically with steroid receptor coactivator-1 to enhance steroid receptor-dependent transcription. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B. O’Malley,et al.  Sequence and Characterization of a Coactivator for the Steroid Hormone Receptor Superfamily , 1995, Science.

[4]  R. Harrison,et al.  Characterization of a monoclonal antibody to the rat liver glucocorticoid receptor. , 1984, Endocrinology.

[5]  Andrew J. Bannister,et al.  The CBP co-activator is a histone acetyltransferase , 1996, Nature.

[6]  T. Archer,et al.  Nucleosome-mediated disruption of transcription factor-chromatin initiation complexes at the mouse mammary tumor virus long terminal repeat in vivo , 1994, Molecular and cellular biology.

[7]  D. Edwards,et al.  Immunologic analysis of human breast cancer progesterone receptors. 1. Immunoaffinity purification of transformed receptors and production of monoclonal antibodies. , 1987, Biochemistry.

[8]  Christopher K. Glass,et al.  The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function , 1997, Nature.

[9]  B. Howard,et al.  The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases , 1996, Cell.

[10]  P. Chambon,et al.  TIF2, a 160 kDa transcriptional mediator for the ligand‐dependent activation function AF‐2 of nuclear receptors. , 1996, The EMBO journal.

[11]  Thorsten Heinzel,et al.  A CBP Integrator Complex Mediates Transcriptional Activation and AP-1 Inhibition by Nuclear Receptors , 1996, Cell.

[12]  M. Yaniv,et al.  A human homologue of Saccharomyces cerevisiae SNF2/SWI2 and Drosophila brm genes potentiates transcriptional activation by the glucocorticoid receptor. , 1993, The EMBO journal.

[13]  G. Hager,et al.  Glucocorticoid receptor-dependent disruption of a specific nucleosome on the mouse mammary tumor virus promoter is prevented by sodium butyrate. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[14]  G. Hager,et al.  Transcription factor loading on the MMTV promoter: a bimodal mechanism for promoter activation. , 1992, Science.

[15]  Sushovan Guha,et al.  The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest , 1994, Cell.

[16]  M. Beato,et al.  Hormone induces binding of receptors and transcription factors to a rearranged nucleosome on the MMTV promoter in vivo. , 1995, The EMBO journal.

[17]  V. Moudgil,et al.  Novel antiprogestins Org 31806 and 31710: Interaction with mammalian progesterone receptor and DNA binding of antisteroid receptor complexes , 1992, The Journal of Steroid Biochemistry and Molecular Biology.

[18]  H. Richard-Foy,et al.  Sequence‐specific positioning of nucleosomes over the steroid‐inducible MMTV promoter. , 1987, The EMBO journal.

[19]  G. Crabtree,et al.  Diversity and specialization of mammalian SWI/SNF complexes. , 1996, Genes & development.

[20]  M. Grunstein.  Histone function in transcription. , 1990, Annual review of cell biology.

[21]  I. Herskowitz,et al.  Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid receptors. , 1992, Science.

[22]  J. Mymryk,et al.  Steroid hormone receptor status defines the MMTV promoter chromatin structure in vivo , 1995, The Journal of Steroid Biochemistry and Molecular Biology.

[23]  K. Horwitz,et al.  Nuclear receptor coactivators and corepressors. , 1996, Molecular endocrinology.

[24]  Carl Wu.  Chromatin Remodeling and the Control of Gene Expression* , 1997, The Journal of Biological Chemistry.

[25]  M. Stallcup,et al.  GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[26]  C. Glass,et al.  Nuclear receptor coactivators. , 1997, Current opinion in cell biology.

[27]  R. Kingston,et al.  Repression and activation by multiprotein complexes that alter chromatin structure. , 1996, Genes & development.

[28]  M. Montminy,et al.  Role of CBP/P300 in nuclear receptor signalling , 1996, Nature.

[29]  R. Palmiter,et al.  Butyrate and related inhibitors of histone deacetylation block the induction of egg white genes by steroid hormones , 1980, Cell.

[30]  S. Nordeen,et al.  The differential capacity of glucocorticoids and progestins to alter chromatin structure and induce gene expression in human breast cancer cells. , 1994, Molecular endocrinology.