scholarly journals The full induction of human apoprotein A-I gene expression by the experimental nephrotic syndrome in transgenic mice depends on cis-acting elements in the proximal 256 base-pair promoter region and the trans-acting factor early growth response factor 1.

1998 ◽  
Vol 101 (8) ◽  
pp. 1699-1707 ◽  
Author(s):  
M Zaiou ◽  
N Azrolan ◽  
T Hayek ◽  
H Wang ◽  
L Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nephrotic Syndrome ◽  
Transgenic Mice ◽  
Promoter Region ◽  
Growth Response ◽  
Early Growth ◽  
Response Factor ◽  
Cis Acting ◽  
Early Growth Response ◽  
I Gene

scholarly journals cAMP-response-element-binding-protein-binding protein (CBP) and p300 are transcriptional co-activators of early growth response factor-1 (Egr-1)

1998 ◽  
Vol 336 (1) ◽  
pp. 183-189 ◽  
Author(s):  
Eric S. SILVERMAN ◽  
Jing DU ◽  
Amy J. WILLIAMS ◽  
Raj WADGAONKAR ◽  
Jeffrey M. DRAZEN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Binding ◽  
Growth Response ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Early Growth ◽  
Response Factor ◽  
Camp Response Element ◽  
Early Growth Response ◽  
Element Binding Protein

Egr-1 (early-growth response factor-1) is a sequence-specific transcription factor that plays a regulatory role in the expression of many genes important for cell growth, development and the pathogenesis of disease. The transcriptional co-activators CBP (cAMP-response-element-binding-protein-binding protein) and p300 interact with sequence-specific transcription factors as well as components of the basal transcription machinery to facilitate RNA polymerase II recruitment and transcriptional initiation. Here we demonstrate a unique way in which Egr-1 physically and functionally interacts with CBP/p300 to modulate gene transcription. CBP/p300 potentiated Egr-1 mediated expression of 5-lipoxygenase (5-LO) promoter–reporter constructs, and the degree of trans-activation was proportional to the number of Egr-1 consensus binding sites present in wild-type and naturally occurring mutants of the 5-LO promoter. The N- and C-terminal domains of CBP interact with the transcriptional activation domain of Egr-1, as demonstrated by a mammalian two-hybrid assay. Direct protein–protein interactions between CBP/p300 and Egr-1 were demonstrated by glutathione S-transferase fusion-protein binding and co-immunoprecipitation/Western-blot studies. These data suggest that CBP and p300 act as transcriptional co-activators for Egr-1-mediated gene expression and that variations between individuals in such co-activation could serve as a genetic basis for variability in gene expression.

scholarly journals Early stimulation and late inhibition of peroxisome proliferator-activated receptor gamma (PPARgamma) gene expression by transforming growth factor beta in human aortic smooth muscle cells: role of early growth-response factor-1 (Egr-1), activator protein 1 (AP1) and Smads

2003 ◽  
Vol 370 (3) ◽  
pp. 1019-1025 ◽  
Author(s):  
Mingui FU ◽  
Jifeng ZHANG ◽  
Yimin LIN ◽  
Xiaojun ZHU ◽  
Luning ZHAO ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Response ◽  
Transforming Growth Factor ◽  
Early Growth ◽  
Peroxisome Proliferator ◽  
Response Factor ◽  
Activator Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Early Growth Response ◽  
Pparγ Expression

Transforming growth factor β (TGFβ) and peroxisome proliferator-activated receptor γ (PPARγ) play major roles in the development of vascular diseases. It has been documented that PPARγ activation inhibits the TGFβ signal pathway in vascular smooth muscle cells (VSMC). Here we examined whether TGFβ can regulate PPARγ expression. Northern blot analyses revealed that both TGFβ1 and 2 exert a biphasic effect (early stimulation and late repression) on PPARγ gene expression in VSMC. TGFβ rapidly and transiently induced early growth-response factor-1 (Egr-1) expression through the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 (MEK1)/ERK-mediated pathway. Inhibition of MEK1/ERK by PD98059 not only abrogated the induction of Egr-1 but also abolished the rapid and transient induction of PPARγ by TGFβ. Furthermore, overexpression of NAB2, a repressor of Egr-1 activation, also blocked the induction of PPARγ by TGFβ in VSMC, suggesting that Egr-1 mediates the rapid and transient induction of PPARγ by TGFβ. With regard to the TGFβ repression of PPARγ expression, activator protein 1 (AP1) and Smad3/4 dramatically inhibited the PPARγ promoter activity in transient-transfection studies. In contrast, adenovirus-mediated overexpression of a dominant-negative form of c-Jun partially rescued the TGFβ-induced PPARγ repression in VSMC. Taken together, our data demonstrate that Egr-1, AP1 and Smad are part components of the TGFβ signal transduction pathway that regulates PPARγ expression.

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