CREB-binding Protein and p300 in Transcriptional Regulation*

CREB-binding protein (CBP) and p300 are believed to participate in the activities of hundreds of different transcription factors (see Fig. 1). Current models suggest that the binding of these coactivators to transcription factor activation domains positions histone acetyltransferases (HATs) near specific nucleosomes in target gene promoter regions (for review, see Ref. 1). Interactions with components of the general transcriptional machinery, such as TFIID, TFIIB, and the RNA polymerase II holoenzyme (RNAPII) have also been suggested to contribute to CBP/p300 function. The simultaneous interaction of multiple transcription factors with CBP/p300 has been proposed to contribute to transcriptional synergy. Conversely, competition for CBP/p300 binding has been suggested to mediate some examples of signal-induced transcriptional repression. An overview of CBP/p300 in cellular growth and differentiation has recently been published (2), but many questions regarding their role in transcriptional regulation remain unanswered. This review deals with some of the more controversial aspects of CBP/p300 function. In particular, we will ask whether CBP and p300 have distinct functions, review the evidence for their regulation by phosphorylation, and ask whether they function primarily by acetylating histones or other proteins. We will also revisit the evidence for the role of CBP/p300 as transcriptional “integrators.” Finally, we will attempt to localize CBP/p300 function within the complex series of processes involved in transcriptional activation.

[1]  G. Nabel,et al.  Modulation of cytokine‐induced HIV gene expression by competitive binding of transcription factors to the coactivator p300 , 1998, The EMBO journal.

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

[3]  Andrew J. Bannister,et al.  The acetyltransferase activity of CBP stimulates transcription , 1998, The EMBO journal.

[4]  Tae Hoon Kim,et al.  Efficient recruitment of TFIIB and CBP-RNA polymerase II holoenzyme by an interferon-beta enhanceosome in vitro. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[5]  K. Senger,et al.  Mechanism by which the IFN-beta enhanceosome activates transcription. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Tjian,et al.  Composite co-activator ARC mediates chromatin-directed transcriptional activation , 1999, Nature.

[7]  L. Kedes,et al.  Differential roles of p300 and PCAF acetyltransferases in muscle differentiation. , 1997, Molecular cell.

[8]  M. Merika,et al.  Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic activation of transcription. , 1998, Molecular cell.

[9]  Wei Gu,et al.  Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain , 1997, Cell.

[10]  Mariann Bienz,et al.  Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling , 1998, Nature.

[11]  R. Goodman,et al.  Histone Binding Protein RbAp48 Interacts with a Complex of CREB Binding Protein and Phosphorylated CREB , 2000, Molecular and Cellular Biology.

[12]  R. Evans,et al.  Regulation of Hormone-Induced Histone Hyperacetylation and Gene Activation via Acetylation of an Acetylase , 1999, Cell.

[13]  T. Maniatis,et al.  Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. , 1998, Molecular cell.

[14]  Raoul C. M. Hennekam,et al.  Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP , 1995, Nature.

[15]  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.

[16]  J. Craig,et al.  Recruitment of CREB Binding Protein Is Sufficient for CREB-Mediated Gene Activation , 2000, Molecular and Cellular Biology.

[17]  R. Roeder,et al.  Transcriptional regulation through Mediator-like coactivators in yeast and metazoan cells. , 2000, Trends in biochemical sciences.

[18]  A. Nordheim,et al.  MAP kinase-dependent transcriptional coactivation by Elk-1 and its cofactor CBP. , 1996, Biochemical and biophysical research communications.

[19]  David Newsome,et al.  Gene Dosage–Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300 , 1998, Cell.

[20]  M. Muramatsu,et al.  p300-mediated acetylation facilitates the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone. , 2000, Genes & development.

[21]  J. Yu,et al.  Three unrelated viral transforming proteins (vIRF, EBNA2, and E1A) induce the MYC oncogene through the interferon-responsive PRF element by using different transcription coadaptors. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[22]  C. Allis,et al.  The language of covalent histone modifications , 2000, Nature.

[23]  Y. Nakatani,et al.  ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation , 2000, Nature.

[24]  C. Hui,et al.  Developmentally regulated expression of the transcriptional cofactors/histone acetyltransferases CBP and p300 during mouse embryogenesis. , 1999, The International journal of developmental biology.

[25]  J. Chrivia,et al.  CREB-binding Protein Activates Transcription through Multiple Domains* , 1996, The Journal of Biological Chemistry.

[26]  K. Senger,et al.  Acetylation of HMG I(Y) by CBP turns off IFN beta expression by disrupting the enhanceosome. , 1998, Molecular cell.

[27]  C. Allis,et al.  Cell cycle-regulated histone acetylation required for expression of the yeast HO gene. , 1999, Genes & development.

[28]  D. Livingston,et al.  Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell differentiation , 1998, Nature.

[29]  J. Girault,et al.  Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A , 1998, Nature.

[30]  P. Yaciuk,et al.  Simian virus 40 large-T antigen expresses a biological activity complementary to the p300-associated transforming function of the adenovirus E1A gene products , 1991, Molecular and cellular biology.

[31]  C. Allis,et al.  Transcription regulation in eukaryotes , 1999 .

[32]  M. Bustin,et al.  Acetylation of Novel Sites in the Nucleosomal Binding Domain of Chromosomal Protein HMG-14 by p300 Alters Its Interaction with Nucleosomes* , 2000, The Journal of Biological Chemistry.

[33]  D. Livingston,et al.  Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. , 2000, Genes & development.

[34]  Anirvan Ghosh,et al.  Regulation of CBP-Mediated Transcription by Neuronal Calcium Signaling , 1999, Neuron.

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

[36]  M. Montminy,et al.  Characterization of a CREB Gain-of-Function Mutant with Constitutive Transcriptional Activity In Vivo , 2000, Molecular and Cellular Biology.

[37]  H. Ugai,et al.  The coactivators p300 and CBP have different functions during the differentiation of F9 cells , 1999, Journal of Molecular Medicine.

[38]  D. Sterner,et al.  Acetylation of Histones and Transcription-Related Factors , 2000, Microbiology and Molecular Biology Reviews.

[39]  H. Bading,et al.  Control of Recruitment and Transcription-Activating Function of CBP Determines Gene Regulation by NMDA Receptors and L-Type Calcium Channels , 1999, Neuron.

[40]  R. Goodman,et al.  CBP/p300 in cell growth, transformation, and development. , 2000, Genes & development.

[41]  R. Kingston.  A shared but complex bridge , 1999, Nature.

[42]  R. Roeder,et al.  HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF. , 2000, Molecular cell.

[43]  M. Merika,et al.  The role of HMG I(Y) in the assembly and function of the IFN‐β enhanceosome , 1999, The EMBO journal.

[44]  F. Gage,et al.  The Signal-Dependent Coactivator CBP Is a Nuclear Target for pp90RSK , 1996, Cell.

[45]  R. Roeder,et al.  Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[46]  C. Glass,et al.  Signal-specific co-activator domain requirements for Pit-1 activation , 1998, Nature.

[47]  G. Nabel,et al.  Regulation of NF-κB by Cyclin-Dependent Kinases Associated with the p300 Coactivator , 1997, Science.

[48]  R. Roeder,et al.  Thyroid hormone receptor-associated proteins and general positive cofactors mediate thyroid hormone receptor function in the absence of the TATA box-binding protein-associated factors of TFIID. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[49]  H. Bading,et al.  CBP: a signal-regulated transcriptional coactivator controlled by nuclear calcium and CaM kinase IV. , 1998, Science.

[50]  Michael E. Greenberg,et al.  Coupling of the RAS-MAPK Pathway to Gene Activation by RSK2, a Growth Factor-Regulated CREB Kinase , 1996, Science.

[51]  K. Nasmyth,et al.  Ordered Recruitment of Transcription and Chromatin Remodeling Factors to a Cell Cycle– and Developmentally Regulated Promoter , 2016, Cell.