scholarly journals A Role for CREB Binding Protein and p300 Transcriptional Coactivators in Ets-1 Transactivation Functions

1998 ◽  
Vol 18 (4) ◽  
pp. 2218-2229 ◽  
Author(s):  
Cheng Yang ◽  
Linda H. Shapiro ◽  
Morris Rivera ◽  
Alok Kumar ◽  
Paul K. Brindle
Keyword(s):  
Binding Protein ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Creb Binding Protein ◽  
Rich Region ◽  
Adenovirus E1a ◽  
Synergistic Interactions ◽  
Nuclear Complex ◽  
Transcriptional Coactivators ◽  
Histone Acetyltransferase Activity

ABSTRACT The Ets-1 transcription factor plays a critical role in cell growth and development, but the means by which it activates transcription are still unclear (J. C. Bories, D. M. Willerford, D. Grevin, L. Davidson, A. Camus, P. Martin, D. Stehelin, F. W. Alt, and J. C. Borles, Nature 377:635–638, 1995; N. Muthusamy, K. Barton, and J. M. Leiden, Nature 377:639–642, 1995). Here we show that Ets-1 binds the transcriptional coactivators CREB binding protein (CBP) and the related p300 protein (together referred to as CBP/p300) and that this interaction is required for specific Ets-1 transactivation functions. The Ets-1- and c-Myb-dependent aminopeptidase N (CD13/APN) promoter and an Ets-1-dependent artificial promoter were repressed by adenovirus E1A, a CBP/p300-specific inhibitor. Furthermore, Ets-1 activity was potentiated by CBP and p300 overexpression. The transactivation function of Ets-1 correlated with its ability to bind an N-terminal cysteine- and histidine-rich region spanning CBP residues 313 to 452. Ets-1 also bound a second cysteine- and histidine-rich region of CBP, between residues 1449 and 1892. Both Ets-1 and CBP/p300 formed a stable immunoprecipitable nuclear complex, independent of DNA binding. This Ets-1–CBP/p300 immunocomplex possessed histone acetyltransferase activity, consistent with previous findings that CBP/p300 is associated with such enzyme activity. Our results indicate that CBP/p300 may mediate antagonistic and synergistic interactions between Ets-1 and other transcription factors that use CBP/p300 as a coactivator, including c-Myb and AP-1.

scholarly journals p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor

2003 ◽  
Vol 369 (3) ◽  
pp. 477-484 ◽  
Author(s):  
Antonio De LUCA ◽  
Anna SEVERINO ◽  
Paola De PAOLIS ◽  
Giuliano COTTONE ◽  
Luca De LUCA ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Creb Binding Protein ◽  
Camp Response Element ◽  
Response Element ◽  
Adenovirus E1a ◽  
Element Binding Protein ◽  
Enhancer Factor

Thyroid hormone receptors (TRs) and members of the myocyte enhancer factor 2 (MEF2) family are involved in the regulation of muscle-specific gene expression during myogenesis. Physical interaction between these two factors is required to synergistically activate gene transcription. p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) interacting with transcription factors is able to increase their activity on target gene promoters. We investigated the role of p300 in regulating the TR—MEF2A complex. To this end, we mapped the regions of these proteins involved in physical interactions and we evaluated the expression of a chloramphenicol acetyltransferase (CAT) reporter gene in U2OS cells under control of the α-myosin heavy chain promoter containing the thyroid hormone response element (TRE). Our results suggested a role of p300/CBP in mediating the transactivation effects of the TR—retenoid X receptor (RxR)—MEF2A complex. Our findings showed that the same C-terminal portion of p300 binds the N-terminal domains of both TR and MEF2A, and our in vivo studies demonstrated that TR, MEF2A and p300 form a ternary complex. Moreover, by the use of CAT assays, we demonstrated that adenovirus E1A inhibits activation of transcription by TR—RxR—MEF2A—p300 but not by TR—RxR—MEF2A. Our data suggested that p300 can bind and modulate the activity of TR—RxR—MEF2A at TRE. In addition, it is speculated that p300 might modulate the activity of the TR—RxR—MEF2A complex by recruiting a hypothetical endogenous inhibitor which may act like adenovirus E1A.

scholarly journals p300/CREB Binding Protein-Related Protein p270 Is a Component of Mammalian SWI/SNF Complexes

1998 ◽  
Vol 18 (6) ◽  
pp. 3596-3603 ◽  
Author(s):  
Peter B. Dallas ◽  
Ian Wayne Cheney ◽  
Da-Wei Liao ◽  
Valerie Bowrin ◽  
Whitney Byam ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Binding Protein ◽  
Chromatin Modification ◽  
Cellular Protein ◽  
Cellular Proteins ◽  
Creb Binding Protein ◽  
Detailed Characterization ◽  
Molecular Masses ◽  
Histone Acetyltransferase Activity

ABSTRACT p300 and the closely related CREB binding protein (CBP) are transcriptional adaptors that are present in intracellular complexes with TATA binding protein (TBP) and bind to upstream activators including p53 and nuclear hormone receptors. They have intrinsic and associated histone acetyltransferase activity, suggesting that chromatin modification is an essential part of their role in regulating transcription. Detailed characterization of a panel of antibodies raised against p300/CBP has revealed the existence of a 270-kDa cellular protein, p270, distinct from p300 and CBP but sharing at least two independent epitopes with p300. The subset of p300/CBP-derived antibodies that cross-reacts with p270 consistently coprecipitates a series a cellular proteins with relative molecular masses ranging from 44 to 190 kDa. Purification and analysis of various proteins in this group reveals that they are components of the human SWI/SNF complex and that p270 is an integral member of this complex.

scholarly journals Nuclear Factor of Activated T Cells (NFAT)-dependent Transactivation Regulated by the Coactivators p300/CREB-binding Protein (CBP)

1998 ◽  
Vol 187 (12) ◽  
pp. 2031-2036 ◽  
Author(s):  
Carmen García-Rodríguez ◽  
Anjana Rao
Keyword(s):  
T Cells ◽  
Binding Protein ◽  
Critical Role ◽  
Regulation Of Transcription ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Transactivation Domain ◽  
Creb Binding Protein ◽  
Activated T Cells ◽  
Viral Oncoprotein

p300 and cAMP response element–binding protein (CREB)–binding protein (CBP) are members of a family of coactivators involved in the regulation of transcription and chromatin. We show that transcription factors of the nuclear factor of activated T cells (NFAT) family bind p300/CBP and recruit histone acetyltransferase activity from T cell nuclear extracts. The NH2-terminal transactivation domain of NFAT1 and the phospho-CREB- and E1A-binding sites of p300/CBP are involved in the interaction. The viral oncoprotein E1A inhibits NFAT-dependent transactivation in a p300-dependent manner. Recruitment of the coactivators p300/CBP by the transactivation domains of NFAT proteins is likely to play a critical role in NFAT-dependent gene expression during the immune response.

scholarly journals Global transcriptional coactivators CREB-binding protein and p300 are highly essential collectively but not individually in peripheral B cells

Blood ◽  
2006 ◽  
Vol 107 (11) ◽  
pp. 4407-4416 ◽  
Author(s):  
Wu Xu ◽  
Tomofusa Fukuyama ◽  
Paul A. Ney ◽  
Demin Wang ◽  
Jerold Rehg ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Binding Protein ◽  
Cell Receptor ◽  
Conditional Knockout ◽  
Creb Binding Protein ◽  
Cell Stage ◽  
Transcriptional Coactivators ◽  
B Cell Homeostasis ◽  
Peripheral B Cells

Abstract CREB-binding protein (CBP) and its para-log p300 are transcriptional coactivators that physically or functionally interact with over 320 mammalian and viral proteins, including 36 that are essential for B cells in mice. CBP and p300 are generally considered limiting for transcription, yet their roles in adult cell lineages are largely unknown since homozygous null mutations in either gene or compound heterozygosity cause early embryonic lethality in mice. We tested the hypotheses that CBP and p300 are limiting and that each has unique properties in B cells, by using mice with Cre/LoxP conditional knockout alleles for CBP (CBPflox) and p300 (p300flox), which carry CD19Cre that initiates floxed gene recombination at the pro–B-cell stage. CD19Cre-mediated loss of CBP or p300 led to surprisingly modest deficits in B-cell numbers, whereas inactivation of both genes was not tolerated by peripheral B cells. There was a moderate decrease in B-cell receptor (BCR)–responsive gene expression in CBP or p300 homozygous null B cells, suggesting that CBP and p300 are essential for this signaling pathway that is crucial for B-cell homeostasis. These results indicate that individually CBP and p300 are partially limiting beyond the pro-B-cell stage and that other coactivators in B cells cannot replace their combined loss.

Mice Homozygous for a Truncated Form of CREB-Binding Protein Exhibit Defects in Hematopoiesis and Vasculo-angiogenesis

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 2771-2779 ◽  
Author(s):  
Yuichi Oike ◽  
Nobuyuki Takakura ◽  
Akira Hata ◽  
Tadashi Kaname ◽  
Miwa Akizuki ◽  
...  
Keyword(s):  
Network Formation ◽  
Binding Protein ◽  
Neural Tube Closure ◽  
Creb Binding Protein ◽  
Truncated Form ◽  
Adenovirus E1a ◽  
Primitive Hematopoiesis ◽  
Mutant Mouse Embryos ◽  
Homozygous Mutant Mouse ◽  
Endothelial Precursors

CREB-binding protein (CBP) and the closely related adenovirus E1A-associated 300-kD protein (p300) function as coactivators of transcription factors such as CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. To study the roles of CBP in embryonic development, we generated CBP homozygous mutant mouse embryos that expressed a truncated form of CBP protein (1-1084 out of 2441 residues). The embryos died between embryonic days 9.5 (E9.5) and E10.5 and exhibited a defect in neural tube closure. They appeared pale and showed decreases in erythroid cells and colony-forming cells (CFCs) in the yolk sac, suggesting defects in primitive hematopoiesis. Immunohistochemistry with an anti-PECAM antibody showed a lack of vascular network formation. Organ culture of para-aortic splanchnopleural mesoderm (P-Sp) with stromal cells (OP9) showed an autonomous abnormality of putative endothelial precursors, which may induce the microenvironmental defect in hematopoiesis. In addition, these defects were partially rescued by the addition of VEGF to this culture. Our analyses demonstrate that CBP plays an essential role in hematopoiesis and vasculo-angiogenesis.

scholarly journals Site-Specific Acetylation by p300 or CREB Binding Protein Regulates Erythroid Krüppel-Like Factor Transcriptional Activity via Its Interaction with the SWI-SNF Complex

2001 ◽  
Vol 21 (7) ◽  
pp. 2413-2422 ◽  
Author(s):  
Wenjun Zhang ◽  
Shilpa Kadam ◽  
Beverly M. Emerson ◽  
James J. Bieker
Keyword(s):  
Chromatin Structure ◽  
Binding Protein ◽  
Globin Gene ◽  
Critical Role ◽  
Erythroid Cell ◽  
Transactivation Domain ◽  
Creb Binding Protein ◽  
Site Specific ◽  
Acetylation Status

ABSTRACT Recruitment of modifiers and remodelers to specific DNA sites within chromatin plays a critical role in controlling gene expression. The study of globin gene regulation provides a convergence point within which to address these issues in the context of tissue-specific and developmentally regulated expression. In this regard, erythroid Krüppel-like factor (EKLF) is critical. EKLF is a red cell-specific activator whose presence is crucial for establishment of the correct chromatin structure and high-level transcriptional induction of adult β-globin. We now find, by metabolic labeling-immunoprecipitation experiments, that EKLF is acetylated in the erythroid cell. EKLF residues acetylated by CREB binding protein (CBP) in vitro map to Lys-288 in its transactivation domain and Lys-302 in its zinc finger domain. Although site-specific DNA binding by EKLF is unaffected by the acetylation status of either of these lysines, directed mutagenesis of Lys-288 (but not Lys-302) decreases the ability of EKLF to transactivate the β-globin promoter in vivo and renders it unable to be superactivated by coexpressed p300 or CBP. In addition, the acetyltransferase function of CBP or p300 is required for superactivation of wild-type EKLF. Finally, acetylated EKLF has a higher affinity for the SWI-SNF chromatin remodeling complex and is a more potent transcriptional activator of chromatin-assembled templates in vitro. These results demonstrate that the acetylation status of EKLF is critical for its optimal activity and suggest a mechanism by which EKLF acts as an integrator of remodeling and transcriptional components to alter chromatin structure and induce adult β-globin expression within the β-like globin cluster.

Mice Homozygous for a Truncated Form of CREB-Binding Protein Exhibit Defects in Hematopoiesis and Vasculo-angiogenesis

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 2771-2779 ◽  
Author(s):  
Yuichi Oike ◽  
Nobuyuki Takakura ◽  
Akira Hata ◽  
Tadashi Kaname ◽  
Miwa Akizuki ◽  
...  
Keyword(s):  
Network Formation ◽  
Binding Protein ◽  
Neural Tube Closure ◽  
Creb Binding Protein ◽  
Truncated Form ◽  
Adenovirus E1a ◽  
Primitive Hematopoiesis ◽  
Mutant Mouse Embryos ◽  
Homozygous Mutant Mouse ◽  
Endothelial Precursors

Abstract CREB-binding protein (CBP) and the closely related adenovirus E1A-associated 300-kD protein (p300) function as coactivators of transcription factors such as CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. To study the roles of CBP in embryonic development, we generated CBP homozygous mutant mouse embryos that expressed a truncated form of CBP protein (1-1084 out of 2441 residues). The embryos died between embryonic days 9.5 (E9.5) and E10.5 and exhibited a defect in neural tube closure. They appeared pale and showed decreases in erythroid cells and colony-forming cells (CFCs) in the yolk sac, suggesting defects in primitive hematopoiesis. Immunohistochemistry with an anti-PECAM antibody showed a lack of vascular network formation. Organ culture of para-aortic splanchnopleural mesoderm (P-Sp) with stromal cells (OP9) showed an autonomous abnormality of putative endothelial precursors, which may induce the microenvironmental defect in hematopoiesis. In addition, these defects were partially rescued by the addition of VEGF to this culture. Our analyses demonstrate that CBP plays an essential role in hematopoiesis and vasculo-angiogenesis.

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