Steroid receptor coactivator-1 (SRC-1) enhances ligand-dependent and receptor-dependent cell-free transcription of chromatin.

Progesterone receptor (PR) functions as a transcription factor that modulates the transcription of target genes in response to progesterone and other signals. The transcriptional activity of PR requires the involvement of coactivators such as steroid receptor coactivator-1 (SRC-1). To dissect the role of SRC-1 in PR transactivation, we established an in vitro transcription system with chromatin templates, in which PR induced transcription in a ligand-dependent and PRE-dependent manner. In the presence of ligand, purified PR bound to chromatin templates, resulting in chromatin remodeling. With this system, the ability of purified SRC-1 to act as a coactivator of PR was examined. SRC-1 potentiated transcription by ligand-activated PR, whereas it had no effect on transcription in the absence of ligands. As SRC-1 possesses intrinsic histone acetyltransferase activity, we tested the role of acetylation in PR-mediated transcription by using a histone deacetylase inhibitor, trichostatin A (TSA). We found that addition of TSA strongly enhanced PR-dependent transcription on chromatin but not on naked DNA template, and the effects of SRC-1 and TSA on PR transactivation were partially redundant. In addition, SRC-1 was able to potentiate PR transactivation with nonchromatin templates. Thus, our results substantiate a two-step mechanism whereby recruitment of coactivator SRC-1 by the ligand-activated PR in vivo leads to (i) chromatin remodeling through histone acetylation and (ii) recruitment/stabilization of the preinitiation complex.

[1]  R. Lanz,et al.  Nuclear receptor coregulators: cellular and molecular biology. , 1999, Endocrine reviews.

[2]  Paul Tempst,et al.  Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex , 1999, Nature.

[3]  L. Freedman.  Increasing the Complexity of Coactivation in Nuclear Receptor Signaling , 1999, Cell.

[4]  C. Glass,et al.  Coactivator and corepressor complexes in nuclear receptor function. , 1999, Current opinion in genetics & development.

[5]  P. Chambon,et al.  Ligand-dependent activation of transcription in vitro by retinoic acid receptor α/retinoid X receptor α heterodimers that mimics transactivation by retinoids in vivo , 1999 .

[6]  N. McKenna,et al.  Distinct steady-state nuclear receptor coregulator complexes exist in vivo. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[7]  T. Archer,et al.  Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex , 1998, Nature.

[8]  K. Struhl.  Histone acetylation and transcriptional regulatory mechanisms. , 1998, Genes & development.

[9]  J. T. Kadonaga.  Eukaryotic Transcription: An Interlaced Network of Transcription Factors and Chromatin-Modifying Machines , 1998, Cell.

[10]  J. T. Kadonaga,et al.  p300 and estrogen receptor cooperatively activate transcription via differential enhancement of initiation and reinitiation. , 1998, Genes & development.

[11]  M. Grunstein.  Histone acetylation in chromatin structure and transcription , 1997, Nature.

[12]  C. Allis,et al.  Steroid receptor coactivator-1 is a histone acetyltransferase , 1997, Nature.

[13]  R. Evans,et al.  Nuclear Receptor Coactivator ACTR Is a Novel Histone Acetyltransferase and Forms a Multimeric Activation Complex with P/CAF and CBP/p300 , 1997, Cell.

[14]  G. Jenster,et al.  Steroid receptor induction of gene transcription: a two-step model. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[15]  A. Wolffe,et al.  Histone acetylation: chromatin in action. , 1997, Trends in biochemical sciences.

[16]  M. Beato,et al.  Interaction of steroid hormone receptors with the transcription initiation complex. , 1996, Endocrine reviews.

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

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

[19]  D. Livingston,et al.  The nuclear hormone receptor coactivator SRC-1 is a specific target of p300. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. Takeshita,et al.  Molecular cloning and properties of a full-length putative thyroid hormone receptor coactivator. , 1996, Endocrinology.

[21]  B. Howard,et al.  A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A , 1996, Nature.

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

[23]  K. Umesono,et al.  The nuclear receptor superfamily: The second decade , 1995, Cell.

[24]  Miguel Beato,et al.  Steroid hormone receptors: Many Actors in search of a plot , 1995, Cell.

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

[26]  J. Mymryk,et al.  Dissection of progesterone receptor-mediated chromatin remodeling and transcriptional activation in vivo. , 1995, Genes & development.

[27]  M. Pazin,et al.  ATP-dependent nucleosome reconfiguration and transcriptional activation from preassembled chromatin templates. , 1994, Science.

[28]  G. Martin,et al.  Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription. , 1994, Science.

[29]  A. Wolffe.  The transcription of chromatin templates. , 1994, Current opinion in genetics & development.

[30]  J. T. Kadonaga,et al.  Potentiation of RNA polymerase II transcription by Gal4-VP16 during but not after DNA replication and chromatin assembly. , 1993, Genes & development.

[31]  B. O’Malley,et al.  Members of the steroid hormone receptor superfamily interact with TFIIB (S300-II). , 1992, The Journal of biological chemistry.

[32]  B. O’Malley,et al.  Hormone activation of baculovirus expressed progesterone receptors. , 1992, The Journal of biological chemistry.

[33]  B. O’Malley,et al.  Progesterone enhances target gene transcription by receptor free of heat shock proteins hsp90, hsp56, and hsp70 , 1991, Molecular and cellular biology.

[34]  B. O’Malley,et al.  Identification of a functional intermediate in receptor activation in progesterone-dependent cell-free transcription , 1990, Nature.

[35]  B. O’Malley,et al.  Regulation of in vitro transcription by progesterone receptor. Characterization and kinetic studies. , 1990, The Journal of biological chemistry.

[36]  B. O’Malley,et al.  The progesterone receptor stimulates cell-free transcription by enhancing the formation of a stable preinitiation complex , 1990, Cell.

[37]  P. Chambon,et al.  Steroid hormone receptors compete for factors that mediate their enhancer function , 1989, Cell.

[38]  D. Edwards,et al.  Steroid hormone-dependent interaction of human progesterone receptor with its target enhancer element. , 1988, Molecular endocrinology.

[39]  G. Schütz,et al.  A DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[40]  R. Roeder,et al.  Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. , 1983, Nucleic acids research.

[41]  H. Gould.  Chromatin : a practical approach , 1998 .

[42]  E. Baulieu.  Neurosteroids: of the nervous system, by the nervous system, for the nervous system. , 1997, Recent progress in hormone research.

[43]  B. O’Malley,et al.  Molecular mechanisms of action of steroid/thyroid receptor superfamily members. , 1994, Annual review of biochemistry.

[44]  Liu Et Al , 2022 .