Upstream stimulatory factor 1 transactivates the human gene promoter of the cardiac isoform of acetyl-CoA carboxylase

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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Promoter I of the ovine acetyl-CoA carboxylase-α gene: an E-box motif at −114 in the proximal promoter binds upstream stimulatory factor (USF)-1 and USF-2 and acts as an insulin-response sequence in differentiating adipocytes

Biochemical Journal ◽

10.1042/bj3590273 ◽

2001 ◽

Vol 359 (2) ◽

pp. 273-284 ◽

Cited By ~ 19

Author(s):

Maureen T. TRAVERS ◽

Amanda J. VALLANCE ◽

Helen T. GOURLAY ◽

Clare A. GILL ◽

Izabella KLEIN ◽

...

Keyword(s):

Hepg2 Cells ◽

Binding Protein ◽

Proximal Promoter ◽

Luciferase Reporter ◽

Acetyl Coa Carboxylase ◽

Upstream Stimulatory Factor ◽

Acetyl Coa ◽

Rnase Protection ◽

E Box ◽

Stimulatory Factor

Acetyl-CoA carboxylase-α (ACC-α) plays a central role in co-ordinating de novo fatty acid synthesis in animal tissues. We have characterized the regulatory region of the ovine ACC-α gene. Three promoters, PI, PII and PIII, are dispersed throughout 50kb of genomic DNA. Expression from PI is limited to adipose tissue and liver. Sequence comparison of the proximal promoters of ovine and mouse PIs demonstrates high nucleotide identity and that they are characterized by a TATA box at −29, C/EBP (CCAAT enhancer-binding protein)-binding motifs and multiple E-box motifs. A 4.3kb ovine PI-luciferase reporter construct is insulin-responsive when transfected into differentiated ovine adipocytes, whereas when this construct is transfected into ovine preadipocytes and HepG2 cells the construct is inactive and is not inducible by insulin. By contrast, transfection of a construct corresponding to 132bp of the proximal promoter linked to a luciferase reporter is active and inducible by insulin in all three cell systems. Insulin signalling to the −132bp construct in differentiated ovine adipocytes involves, in part, an E-box motif at −114. Upstream stimulatory factor (USF)-1 and USF-2, but not sterol regulatory element-binding protein 1 (SREBP-1), are major components of protein complexes that bind this E-box motif. Activation of the 4.3kb PI construct in differentiated ovine adipocytes is associated with endogenous expression of PI transcripts throughout differentiation; PI transcripts are not detectable by RNase-protection assay in ovine preadipocytes, HepG2 cells or 3T3-F442A adipocytes. These data indicate the presence of repressor motifs in PI that are required to be de-repressed during adipocyte differentiation to allow induction of the promoter by insulin.

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Promoter I of the ovine acetyl-CoA carboxylase-α gene: an E-box motif at −114 in the proximal promoter binds upstream stimulatory factor (USF)-1 and USF-2 and acts as an insulin-response sequence in differentiating adipocytes

Biochemical Journal ◽

10.1042/0264-6021:3590273 ◽

2001 ◽

Vol 359 (2) ◽

pp. 273 ◽

Cited By ~ 14

Author(s):

Maureen T. TRAVERS ◽

Amanda J. VALLANCE ◽

Helen T. GOURLAY ◽

Clare A. GILL ◽

Izabella KLEIN ◽

...

Keyword(s):

Insulin Response ◽

Response Sequence ◽

Proximal Promoter ◽

Acetyl Coa Carboxylase ◽

Upstream Stimulatory Factor ◽

Acetyl Coa ◽

E Box ◽

Stimulatory Factor

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A novel promoter polymorphism in the human gene GNAS affects binding of transcription factor upstream stimulatory factor 1, Gαs protein expression and body weight regulation

Pharmacogenetics and Genomics ◽

10.1097/fpc.0b013e3282f49964 ◽

2008 ◽

Vol 18 (2) ◽

pp. 141-151 ◽

Cited By ~ 17

Author(s):

Ulrich H. Frey ◽

Hans Hauner ◽

Karl-Heinz Jöckel ◽

Iris Manthey ◽

Norbert Brockmeyer ◽

...

Keyword(s):

Transcription Factor ◽

Body Weight ◽

Protein Expression ◽

Human Gene ◽

Promoter Polymorphism ◽

Weight Regulation ◽

Body Weight Regulation ◽

Upstream Stimulatory Factor ◽

Upstream Stimulatory Factor 1 ◽

Stimulatory Factor

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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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