Histone Acetylation and Recruitment of Serum Responsive Factor and CREB-Binding Protein Onto SM22 Promoter During SM22 Gene Expression

ABSTRACT CREB-binding protein (CBP) is a coactivator for multiple transcription factors that transduce a variety of signaling pathways. Current models propose that CBP enhances gene expression by bridging the signal-responsive transcription factors with components of the basal transcriptional machinery and by augmenting the access of transcription factors to DNA through the acetylation of histones. To define the pathways and proteins that require CBP function in a living organism, we have begun a genetic analysis of CBP in flies. We have overproduced Drosophila melanogaster CBP (dCBP) in a variety of cell types and obtained distinct adult phenotypes. We used an uninflated-wing phenotype, caused by the overexpression of dCBP in specific central nervous system cells, to screen for suppressors of dCBP overactivity. Two genes with mutant versions that act as dominant suppressors of the wing phenotype were identified: thePKA-C1/DCO gene, encoding the catalytic subunit of cyclic AMP protein kinase, and ash1, a member of thetrithorax group (trxG) of chromatin modifiers. Using immunocolocalization, we showed that the ASH1 protein is specifically expressed in the majority of the dCBP-overexpressing cells, suggesting that these proteins have the potential to interact biochemically. This model was confirmed by the findings that the proteins interact strongly in vitro and colocalize at specific sites on polytene chromosomes. The trxG proteins are thought to maintain gene expression during development by creating domains of open chromatin structure. Our results thus implicate a second class of chromatin-associated proteins in mediating dCBP function and imply that dCBP might be involved in the regulation of higher-order chromatin structure.

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Transcriptional Activation by NF-κB Requires Multiple Coactivators

Molecular and Cellular Biology ◽

10.1128/mcb.19.9.6367 ◽

1999 ◽

Vol 19 (9) ◽

pp. 6367-6378 ◽

Cited By ~ 321

Author(s):

Kelly-Ann Sheppard ◽

David W. Rose ◽

Zaffar K. Haque ◽

Riki Kurokawa ◽

Eileen McInerney ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Activation ◽

Histone Acetyltransferase ◽

Binding Protein ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Creb Binding Protein ◽

Element Binding Protein ◽

Cyclic Amp Response Element ◽

Coactivator Complex

ABSTRACT Nuclear factor-κB (NF-κB) plays a role in the transcriptional regulation of genes involved in inflammation and cell survival. In this report we demonstrate that NF-κB recruits a coactivator complex that has striking similarities to that recruited by nuclear receptors. Inactivation of either cyclic AMP response element binding protein (CREB)-binding protein (CBP), members of the p160 family of coactivators, or the CBP-associated factor (p/CAF) by nuclear antibody microinjection prevents NF-κB-dependent transactivation. Like nuclear receptor-dependent gene expression, NF-κB-dependent gene expression requires specific LXXLL motifs in one of the p160 family members, and enhancement of NF-κB activity requires the histone acetyltransferase (HAT) activity of p/CAF but not that of CBP. This coactivator complex is differentially recruited by members of the Rel family. The p50 homodimer fails to recruit coactivators, although the p50-p65 heterodimeric form of the transcription factor assembles the integrator complex. These findings provide new mechanistic insights into how this family of dimeric transcription factors has a differential effect on gene expression.

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The Transcription Factor GLI1 Interacts with SMAD Proteins to Modulate Transforming Growth Factor β-Induced Gene Expression in a p300/CREB-binding Protein-associated Factor (PCAF)-dependent Manner

Journal of Biological Chemistry ◽

10.1074/jbc.m113.545194 ◽

2014 ◽

Vol 289 (22) ◽

pp. 15495-15506 ◽

Cited By ~ 30

Author(s):

Monica D. Nye ◽

Luciana L. Almada ◽

Maite G. Fernandez-Barrena ◽

David L. Marks ◽

Sherine F. Elsawa ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Growth Factor ◽

Transforming Growth Factor ◽

Binding Protein ◽

Transforming Growth Factor Β ◽

Dependent Manner ◽

Creb Binding Protein ◽

Associated Factor ◽

Smad Proteins

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Transcriptional Co-activators CREB-binding Protein and p300 Regulate Chondrocyte-specific Gene Expression via Association with Sox9

Journal of Biological Chemistry ◽

10.1074/jbc.m303471200 ◽

2003 ◽

Vol 278 (29) ◽

pp. 27224-27229 ◽

Cited By ~ 142

Author(s):

Masanao Tsuda ◽

Shigeru Takahashi ◽

Yuji Takahashi ◽

Hiroshi Asahara

Keyword(s):

Gene Expression ◽

Binding Protein ◽

Specific Gene ◽

Creb Binding Protein ◽

Specific Gene Expression

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Selective DNA Binding and Association with the CREB Binding Protein Coactivator Contribute to Differential Activation of Alpha/Beta Interferon Genes by Interferon Regulatory Factors 3 and 7

Molecular and Cellular Biology ◽

10.1128/mcb.20.17.6342-6353.2000 ◽

2000 ◽

Vol 20 (17) ◽

pp. 6342-6353 ◽

Cited By ~ 213

Author(s):

Rongtuan Lin ◽

Pierre Génin ◽

Yaël Mamane ◽

John Hiscott

Keyword(s):

Gene Expression ◽

Dna Binding ◽

Binding Site ◽

Binding Protein ◽

Creb Binding Protein ◽

Regulatory Factors ◽

Transactivation Activity ◽

Dna Binding Site ◽

Alpha Beta ◽

Selective Dna Binding

ABSTRACT Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of the alpha/beta IFN (IFN-α/β) genes as well as the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1, and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4, IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric proteins containing combinations of different IRF-7 and IRF-3 domains were also tested, and the results provided evidence of distinct DNA binding properties of IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB binding protein (CBP) coactivator. Interestingly, some of these fusion proteins led to supraphysiological levels of IFN promoter activation. DNA binding site selection studies demonstrated that IRF-3 and IRF-7 bound to the 5′-GAAANNGAAANN-3′ consensus motif found in many virus-inducible genes; however, a single nucleotide substitution in either of the GAAA half-site motifs eliminated IRF-3 binding and transactivation activity but did not affect IRF-7 interaction or transactivation activity. These studies demonstrate that IRF-3 possesses a restricted DNA binding site specificity and interacts with CBP, whereas IRF-7 has a broader DNA binding specificity that contributes to its capacity to stimulate delayed-type IFN gene expression. These results provide an explanation for the differential regulation of IFN-α/β gene expression by IRF-3 and IRF-7 and suggest that these factors have complementary rather than redundant roles in the activation of the IFN-α/β genes.

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Estradiol attenuates hypoxia-induced pulmonary endothelin-1 gene expression

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00476.2001 ◽

2002 ◽

Vol 283 (1) ◽

pp. L86-L93 ◽

Cited By ~ 48

Author(s):

Scott Earley ◽

Thomas C. Resta

Keyword(s):

Gene Expression ◽

Binding Protein ◽

Barometric Pressure ◽

Camp Response Element Binding ◽

Hypoxic Exposure ◽

Mrna Levels ◽

Creb Binding Protein ◽

Endothelin 1 ◽

Hypoxic Induction ◽

Ovx Rats

The ovarian hormone 17β-estradiol (E2β) attenuates chronic hypoxia-induced pulmonary hypertension. We hypothesized that E2β attenuates this response to hypoxia by decreasing pulmonary expression of the vasoactive and mitogenic peptide endothelin-1 (ET-1). To test this hypothesis, we measured preproET-1 mRNA and ET-1 peptide levels in the lungs of adult female normoxic and hypoxic (24 h or 4 wk at barometric pressure = 380 mmHg) rats with intact ovaries and in hypoxic ovariectomized (OVX) rats administered E2β or vehicle via subcutaneous osmotic pumps. Hypoxic exposure increased lung preproET-1 mRNA levels in OVX vehicle-treated rats, but not in rats with intact ovaries. In addition, E2β replacement prevented hypoxia-mediated increases in preproET-1 mRNA and ET-1 peptide expression. Considering that hypoxic induction of ET-1 gene expression is mediated by a hypoxia-inducible transcription factor(s) (HIF), we further hypothesized that E2β-induced attenuation of pulmonary ET-1 expression during hypoxia results from decreased HIF activity. We found that E2β abolished HIF-dependent increases in reporter gene activity. Further experiments demonstrated that overexpression of the transcriptional coactivator cAMP response element binding protein (CREB) binding protein (CBP)/p300, a factor common to both the estrogen receptor and HIF pathways, eliminated E2β-mediated attenuation of hypoxia-induced ET-1 promoter activity. We conclude that E2β inhibits hypoxic induction of ET-1 gene expression by interfering with HIF activity, possibly through competition for limiting quantities of CBP/p300.

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