Sequential recruitment of steroid receptor coactivator-1 (SRC-1) and p300 enhances progesterone receptor-dependent initiation and reinitiation of transcription from chromatin

Employing a cell-free chromatin transcription system that recapitulates progesterone receptor (PR)-mediated transcription in vivo, we have investigated further the coactivator functions of steroid receptor coactivator-1 (SRC-1) in terms of its functional domains as well as cooperation with other coactivators in PR transactivation. By analyzing wild-type and mutant SRC-1 with liganded PR in the chromatin transcription system in vitro, the basic helix–loop–helix/Per-Arnt-Sim domain, the p300-binding domain, and the carboxyl-terminal region (containing the PR-binding site) of SRC-1 were shown to be important for PR transactivation. Although in context of a synthetic promoter its histone acetyltransferase activity was nonessential for PR-mediated transcription, SRC-1 was observed to act synergistically with p300 to enhance PR transactivation from chromatin. Moreover, SRC-1 and p300 were found to function cooperatively to increase the efficiency of productive transcription initiation and reinitiation. Further analysis of synergism between SRC-1 and p300 revealed an obligatory “sequential” recruitment of SRC-1 and p300 to liganded PR. Efficient recruitment of p300 required the presence of SRC-1. In addition, functional analysis of SRC-2 and SRC-3 coactivators indicated that the SRC family modulated PR transactivation from chromatin by a similar mechanism.

[1]  M. Parker,et al.  Functional Interaction between the p160 Coactivator Proteins and the Transcriptional Enhancer Factor Family of Transcription Factors* , 2000, The Journal of Biological Chemistry.

[2]  Shen-Liang Chen,et al.  The steroid receptor coactivator, GRIP-1, is necessary for MEF-2C-dependent gene expression and skeletal muscle differentiation. , 2000, Genes & development.

[3]  C. Glass,et al.  The coregulator exchange in transcriptional functions of nuclear receptors. , 2000, Genes & development.

[4]  J. T. Kadonaga,et al.  Biochemical Analysis of Distinct Activation Functions in p300 That Enhance Transcription Initiation with Chromatin Templates , 1999, Molecular and Cellular Biology.

[5]  B. O’Malley,et al.  Steroid receptor coactivator-1 (SRC-1) enhances ligand-dependent and receptor-dependent cell-free transcription of chromatin. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  D. Aswad,et al.  Regulation of transcription by a protein methyltransferase. , 1999, Science.

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

[8]  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 .

[9]  C. Glass,et al.  Interactions controlling the assembly of nuclear-receptor heterodimers and co-activators , 1998, Nature.

[10]  D. Edwards,et al.  The Steroid Receptor Coactivator-1 Contains Multiple Receptor Interacting and Activation Domains That Cooperatively Enhance the Activation Function 1 (AF1) and AF2 Domains of Steroid Receptors* , 1998, The Journal of Biological Chemistry.

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

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

[16]  David M. Heery,et al.  A signature motif in transcriptional co-activators mediates binding to nuclear receptors , 1997, Nature.

[17]  E. Baulieu,et al.  RU486 (mifepristone): mechanisms of action and clinical uses. , 1997, Annual review of medicine.

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

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

[20]  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.

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

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

[27]  D. Toft,et al.  Steroid receptors and their associated proteins. , 1993, Molecular Endocrinology.

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

[29]  K. Horwitz,et al.  The molecular biology of RU486. Is there a role for antiprogestins in the treatment of breast cancer? , 1992, Endocrine reviews.

[30]  D. Luse,et al.  Abortive initiation by RNA polymerase II in vitro at the adenovirus 2 major late promoter. , 1987, The Journal of biological chemistry.