Interaction of upstream stimulatory factor with the human heme oxygenase gene promoter

The human C/EBP alpha gene promoter shares significant sequence homology with that of the mouse but has a different mechanism of autoregulation. Activation of the murine promoter by direct binding of C/EBP alpha to a site within 200 bp of the transcriptional start was shown to elevate activity by approximately threefold (R. J. Christy, K. H. Kaestner, D. E. Geiman, and M. D. Lane, Proc. Natl. Acad. Sci. USA 88:2593-2597, 1991; K. Legraverend, P. Antonson, P. Flodby, and K. G. Xanthapoulos, Nucleic Acids Res. 21:1735-1742, 1993). Unlike its murine counterpart, the human C/EBP alpha gene promoter does not contain a cis element that binds the C/EBP alpha protein. Neither C/EBP alpha nor C/EBP beta (NF-Il-6) binds the human C/EBP alpha promoter within 437 bp. However, cotransfection studies show that C/EBP alpha stimulates transcription of a reporter gene driven by 437 bp of the C/EBP alpha promoter. Our studies show that the human C/EBP alpha protein stimulates USF to bind to a USF consensus element within C/EBP alpha promoter and activates it by two- to threefold. We propose that the human gene employs the ubiquitously expressed DNA-binding protein factor USF to carry out autoregulation. Autoregulation of the human C/EBP alpha promoter was abolished by deletion of the USF binding site, CACGTG. Expression of human C/EBP beta following transfection did not stimulate USF binding. These studies suggest a mechanism whereby tissue-specific autoregulation can be achieved via a trans-acting factor that is expressed in all cell types. Thus, direct binding of the C/EBP alpha protein to the promoter of the C/EBP alpha gene is not required for autoregulation.

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Involvement of an Upstream Stimulatory Factor as Well as cAMP-responsive Element-binding Protein in the Activation of Brain-derived Neurotrophic Factor Gene Promoter I

Journal of Biological Chemistry ◽

10.1074/jbc.m204784200 ◽

2002 ◽

Vol 277 (39) ◽

pp. 35920-35931 ◽

Cited By ~ 139

Author(s):

Akiko Tabuchi ◽

Hidemichi Sakaya ◽

Tomochika Kisukeda ◽

Hiroshi Fushiki ◽

Masaaki Tsuda

Keyword(s):

Neurotrophic Factor ◽

Binding Protein ◽

Gene Promoter ◽

Brain Derived Neurotrophic Factor ◽

Upstream Stimulatory Factor ◽

Factor Gene ◽

Element Binding Protein ◽

Responsive Element ◽

Stimulatory Factor ◽

Camp Responsive Element Binding

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Upstream Stimulatory Factor Proteins Are Major Components of the Glucose Response Complex of the L-type Pyruvate Kinase Gene Promoter

Journal of Biological Chemistry ◽

10.1074/jbc.270.6.2640 ◽

1995 ◽

Vol 270 (6) ◽

pp. 2640-2643 ◽

Cited By ~ 81

Author(s):

Anne-Marie Lefran¸ois-Martinez ◽

Antoine Martinez ◽

Bénédicte Antoine ◽

Michel Raymondjean ◽

Axel Kahn

Keyword(s):

Pyruvate Kinase ◽

Gene Promoter ◽

Upstream Stimulatory Factor ◽

Kinase Gene ◽

Glucose Response ◽

Stimulatory Factor ◽

Response Complex

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Upstream stimulatory factor regulates expression of the cell cycle-dependent cyclin B1 gene promoter.

Molecular and Cellular Biology ◽

10.1128/mcb.15.5.2782 ◽

1995 ◽

Vol 15 (5) ◽

pp. 2782-2790 ◽

Cited By ~ 85

Author(s):

J P Cogswell ◽

M M Godlevski ◽

M Bonham ◽

J Bisi ◽

L Babiss

Keyword(s):

Cell Cycle ◽

Gene Activation ◽

Gene Promoter ◽

Cyclin B1 ◽

Binding Activity ◽

Upstream Stimulatory Factor ◽

Reporter System ◽

Dna Binding Activity ◽

B1 Gene ◽

Stimulatory Factor

Progression through the somatic cell cycle requires the temporal regulation of cyclin gene expression and cyclin protein turnover. One of the best-characterized examples of this regulation is seen for the B-type cyclins. These cyclins and their catalytic component, cdc2, have been shown to mediate both the entry into and maintenance of mitosis. The cyclin B1 gene has been shown to be expressed between the late S and G2 phases of the cell cycle, while the protein is degraded specifically at interphase via ubiquitination. To understand the molecular basis for transcriptional regulation of the cyclin B1 gene, we cloned the human cyclin B1 gene promoter region. Using a chloramphenicol acetyltransferase reporter system and both stable and transient assays, we have shown that the cyclin B1 gene promoter (extending to -3800 bp relative to the cap site) can confer G2-enhanced promoter activity. Further analysis revealed that an upstream stimulatory factor (USF)-binding site and its cognate transcription factor(s) are critical for expression from the cyclin B1 promoter in cycling HeLa cells. Interestingly, USF DNA-binding activity appears to be regulated in a G2-specific fashion, supporting the idea that USF may play some role in cyclin B1 gene activation. These studies suggest an important link between USF and the cyclin B1 gene, which in part explains how maturation promoting factor complex formation is regulated.

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Synergistic role of specificity proteins and upstream stimulatory factor 1 in transactivation of the mouse carboxylesterase 2/microsomal acylcarnitine hydrolase gene promoter

Biochemical Journal ◽

10.1042/bj20040765 ◽

2004 ◽

Vol 384 (1) ◽

pp. 101-110 ◽

Cited By ~ 28

Author(s):

Tomomi FURIHATA ◽

Masakiyo HOSOKAWA ◽

Tetsuo SATOH ◽

Kan CHIBA

Keyword(s):

Transcription Factors ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Gene Promoter ◽

Nuclear Factor Κb ◽

Tissue Expression ◽

Upstream Stimulatory Factor ◽

Specificity Protein ◽

Upstream Stimulatory Factor 1 ◽

Stimulatory Factor

Mouse carboxylesterase 2 (mCES2), a microsomal acylcarnitine hydrolase, is thought to play some important roles in fatty acid (ester) metabolism, and it is therefore thought that the level of transcription of the mCES2 gene is under tight control. Examination of the tissue expression profiles revealed that mCES2 is expressed in the liver, kidney, small intestine, brain, thymus, lung, adipose tissue and testis. When the mCES2 promoter was cloned and characterized, it was revealed that Sp1 (specificity protein 1) and Sp3 could bind to a GC box, that USF (upstream stimulatory factor) 1 could bind to an E (enhancer) box, and that Sp1 could bind to an NFκB (nuclear factor κB) element in the mCES2 promoter. Co-transfection assays showed that all of these transcription factors contributed synergistically to transactivation of the mCES2 promoter. Taken together, our results indicate that Sp1, Sp3 and USF1 are indispensable factors for transactivation of the mCES2 gene promoter. To our knowledge, this is the first study in which transcription factors that interact with a CES2 family gene have been identified. The results of the present study have provided some clues for understanding the molecular mechanisms regulating mCES2 gene expression, and should be useful for studies aimed at elucidation of physiological functions of mCES2.

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Upstream stimulatory factor regulates Pdx-1 gene expression in differentiated pancreatic β-cells

Biochemical Journal ◽

10.1042/bj3410315 ◽

1999 ◽

Vol 341 (2) ◽

pp. 315-322 ◽

Cited By ~ 21

Author(s):

Jin QIAN ◽

Elizabeth N. KAYTOR ◽

Howard C. TOWLE ◽

L. Karl OLSON

Keyword(s):

Gene Expression ◽

Gene Promoter ◽

Dominant Negative ◽

Mrna Levels ◽

Upstream Stimulatory Factor ◽

Β Cells ◽

Pancreatic Β Cells ◽

Protein Levels ◽

E Box ◽

Stimulatory Factor

The homeobox gene Pdx-1 plays a key role in the development of the pancreas. In the adult, however, expression of the Pdx-1 gene is restricted to pancreatic β-cells and endocrine cells of duodenal epithelium. Recently, the transcription factor, upstream stimulatory factor (USF), has been shown to bind invitro to a mutationally sensitive E-box motif within the 5′-flanking region of the Pdx-1 gene [Sharma, Leonard, Lee, Chapman, Leiter and Montminy (1996) J. Biol. Chem. 271, 2294-2299]. In the present study, we show that USF not only binds to the Pdx-1 gene promoter but also functionally regulates the expression of the Pdx-1 gene in differentiated pancreatic β-cells. Adenovirus-mediated overexpression of a dominant negative form of USF2 decreased binding of endogenous USF to the E-box element by ~ 90%. This reduction in endogenous USF binding led to a greater than 50% decrease in Pdx-1 gene promoter activity, which, in turn, resulted in marked reductions in Pdx-1 mRNA and protein levels. Importantly, the lower Pdx-1 protein levels led to a greater than 50% reduction in Pdx-1 binding activity to the A3 element on the insulin gene promoter, and a significant reduction in insulin mRNA levels. Overall, our results show that USF functionally regulates Pdx-1 gene expression in differentiated pancreatic β-cells and provide the first functional data for a role of USF in the regulation of a normal cellular gene.

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