The helix-loop-helix transcription factor USF (upstream stimulating factor) binds to a regulatory sequence of the human insulin gene enhancer

Read, Martin; Clark, Andrew R.; Docherty, Kevin

doi:10.1042/bj2950233

Cited by 60 publications

(34 citation statements)

References 37 publications

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“…Accordingly, oligonucleotides corresponding to rat rDNA core promoter or USF inhibited both pol I and pol II transcription. The pol I promoter, therefore, belongs to a family of other E-box containing USF-activated cellular promoters that include those of alcohol dehydrogenase (Potter et al, 1991), mouse metallothionein-I (Carthew et al, 1987;Mueller et al, 1988), human heme oxygenase (Sato et al, 1990), human insulin (Read et al, 1993) and human CD2 (Outram and Owen, 1994). In addition to activation of alcohol dehydrogenase, human insulin and CD2 genes, USF is also known to stimulate pol III transcription of U6 small nuclear RNA gene (Li et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

The dual role of helix – loop – helix-zipper protein USF in ribosomal RNA gene transcription in vivo

1997

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We have previously demonstrated that the core promoter of rat ribosomal RNA gene (rDNA) contains an E-box-like sequence to which the core promoter binding factor CPBF binds and that the 44 kDa subunit of this protein is immunologically related to USF1, the helix ± loop ± helix-zipper DNA binding protein. Further, we showed that RNA polymerase I (pol I) transcription in vitro is competed by oligonucleotides containing USF-binding site, which suggested a key role for USF in rDNA transcription. To prove the potential role of USF in pol I transcription in vivo, USF1 and USF2 homodimers and USF1/USF2 heterodimer were overexpressed in CHO cells by transfection of the respective cDNAs. Co-transfection of a plasmid containing rDNA followed by primer extension analysis showed that overexpression of USF1 and USF2 as homodimers resulted in inhibition of rDNA transcription by as much as 85 ± 90% whereas overexpression of USF1/USF2 in the heterodimeric form activated transcription approximately 3.5-fold. Transfection of mutant USF2 cDNA that is devoid of the basic DNA-binding domain produced only minimal inhibition of rDNA transcription. These data show that USF can modulate transcription of rRNA gene in vivo by functioning as a repressor (homodimer) or activator (heterodimer) of pol I transcription in vivo and suggest that inhibition of rDNA transcription may be responsible for the antiproliferative action of USF homodimers.

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Section: Discussionmentioning

confidence: 99%

The dual role of helix – loop – helix-zipper protein USF in ribosomal RNA gene transcription in vivo

1997

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“…The recognition sequence of USF is present in promoters of a number of cellular genes (Bresnick and Felsenfeld, 1993;Chang et al, 1992;Cogswell et al, 1995;Outram and Owen, 1994;Read et al, 1993;Reisman and Rotter, 1993;Wang and Sul, 1995). USF is a member of the bHLHZip family and exhibits closely related characteristics to another bHLHZip family member, Myc.…”

Section: Introductionmentioning

confidence: 99%

Cross-family interaction between the bHLHZip USF and bZip Fra1 proteins results in down-regulation of AP1 activity

Pognonec¹,

Boulukos²,

Aperlo³

et al. 1997

Oncogene

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Heterodimerization among the basic-leucine zipper (bZIP) proteins or among the basic-helix ± loop ± helixleucine zipper (bHLHZip) proteins confers a multitude of combinational activities to these transcription factors. To further examine the function of the bHLHZip protein, USF, we screened for cellular proteins which could directly interact with USF using the yeast two-hybrid system. A bZip protein, Fra1, was found to e ciently interact with USF. USF speci®cally interacts with Fra1 but not with other closely related family members, c-Fos, Fra2, FosB, or with c-Jun. Both the bHLHZip and the N-terminal regions of Fra1 are required for e cient interaction with USF. In vivo association between USF and Fra1 has been demonstrated by co-immunoprecipitation. Expression of exogenous USF led to a decrease in AP1-dependent transcription in F9 cells. Co-expression of exogenous Fra1 restored the AP1 activity in a dosedependent manner. These data show that USF and Fra1 physically and functionally interact demonstrating that cross-talk occurs between factors of distantly related transcription families.

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“…USF1 is also involved in the transcription of apolipoprotein AII (1), CIII (8) and A5 (9), hepatic lipase (10), ATP-binding cassette transporter A1 (11), glucokinase (12), and angiotensinogen (13). Furthermore, USF1 might modulate the expression of insulin by interacting with the enhancer of the insulin gene (14) and has been reported to affect the expression of the islet-specific glucose-6-phosphatase catalytic subunit-related protein (15).…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in the USF1 gene are associated with low-density lipoprotein cholesterol levels and incident type 2 diabetes mellitus in women: results from the MONICA/KORA Augsburg case–cohort study, 1984–2002

Holzapfel

Baumert²,

Grallert³

et al. 2008

European Journal of Endocrinology

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Objective: Upstream transcription factor 1 (USF1) regulates genes of glucose and lipid metabolism. Polymorphisms in the USF1 gene showed association with familial combined hyperlipidemia and lipid parameters. The aim of our study was to examine the associations between USF1 polymorphisms and lipid parameters as well as incident type 2 diabetes mellitus (T2DM) in German Caucasians. Design: We genotyped eight polymorphisms in the USF1 gene in 2067 middle-aged (35-74 years) individuals including 498 incident T2DM cases and 1569 non-cases of the population-based casecohort study from the MONICA/KORA Augsburg project. Methods: Six polymorphisms and their haplotypes were analyzed using multivariable linear regression and Cox proportional hazards models. Results: Polymorphism rs3737787 was inversely associated with incident T2DM in women with decreased risk for female heterozygotes compared with women homozygous for the major allele (Hazard ratioZ0.57; 95% confidence intervals: 0.38-0.87; PZ0.008). After correction for multiple testing, significance remained. Polymorphisms rs3813609 and rs1556259 were significantly associated with reduction in low-density lipoprotein (LDL) cholesterol (p NOM Z0.001; p NOM Z0.00002) in women. Analyses also indicated associations of haplotypes with LDL cholesterol in women, but the association lost statistical significance after correction for multiple testing. Total serum cholesterol (TC) and high-density lipoprotein (HDL) cholesterol were weakly associated (P!0.05) with USF1 polymorphisms in women. No significant associations were found in men. Conclusions:In this large population-based study, statistically significant associations of USF1 polymorphisms with incident T2DM and LDL cholesterol were found in women, but not in men. Genetic variants in the USF1 gene showed weak or no associations with TC and HDL cholesterol.European Journal of Endocrinology 159 407-416

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The helix-loop-helix transcription factor USF (upstream stimulating factor) binds to a regulatory sequence of the human insulin gene enhancer

Cited by 60 publications

References 37 publications

The dual role of helix – loop – helix-zipper protein USF in ribosomal RNA gene transcription in vivo

The dual role of helix – loop – helix-zipper protein USF in ribosomal RNA gene transcription in vivo

Cross-family interaction between the bHLHZip USF and bZip Fra1 proteins results in down-regulation of AP1 activity

Genetic variants in the USF1 gene are associated with low-density lipoprotein cholesterol levels and incident type 2 diabetes mellitus in women: results from the MONICA/KORA Augsburg case–cohort study, 1984–2002

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