5′ end of hmg CoA reductase gene contains sequences responsible for cholesterol-mediated inhibition of transcription

@article{Osborne19855EO,
  title={5′ end of hmg CoA reductase gene contains sequences responsible for cholesterol-mediated inhibition of transcription},
  author={Timothy F. Osborne and Joseph L. Goldstein and Michael S Brown},
  journal={Cell},
  year={1985},
  volume={42},
  pages={203-212}
}
Cholesterol homeostasis is maintained by feedback inhibition of transcription of the gene encoding HMG CoA reductase. To study this mechanism, we joined the 5' end of the hamster reductase gene to the coding region for chloramphenicol acetyltransferase (CAT). The chimeric gene produced high levels of CAT activity in mouse L cells; sterols suppressed expression by 70% to 90%. Sequences responsible for both promotion and inhibition of transcription were distributed over 500 bp extending 300 bp… 
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References

SHOWING 1-10 OF 43 REFERENCES
HMG CoA reductase: A negatively regulated gene with unusual promoter and 5′ untranslated regions
TLDR
The rate-limiting enzyme of cholesterol biosynthesis, HMG CoA reductase, is controlled by negative feedback regulation of transcription, and the 5' untranslated and promoter regions differ from those of previously characterized genes, which may be relevant to the mechanism of expression of "housekeeping" genes, particularly those that are subject to negative feedbackregulation.
Heterogeneity at the 5' termini of mouse dihydrofolate reductase mRNAs. Evidence for multiple promoter regions.
TLDR
Function can be restored with equal transfection frequency when sequences surrounding the 5' CAACT-TAATAA region at -700 or a complete 48-base pair repeat from the region of -148 to -101 are present in the plasmid construct.
Membrane-bound domain of HMG CoA reductase is required for sterol-enhanced degradation of the enzyme
TLDR
It is concluded that the membrane-bound domain of reductase plays a crucial role in the rapid and regulated degradation of this ER protein.
Adenosine deaminase: characterization and expression of a gene with a remarkable promoter.
TLDR
Cosmid clones containing the gene for human adenosine deaminase (ADA) were isolated and it was shown in a functional assay that a stretch of 135 bp immediately preceding the cap site has promoter activity.
Sterols accelerate degradation of hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase encoded by a constitutively expressed cDNA.
TLDR
It is demonstrated that sterols accelerate the degradation of reductase protein independently of any inhibitory effect on the synthesis of the protein, and this decline was caused by a twofold increase in the rate of degradation of preformed enzyme molecules.
Multiple mRNAs for 3-hydroxy-3-methylglutaryl coenzyme A reductase determined by multiple transcription initiation sites and intron splicing sites in the 5'-untranslated region.
The current studies show that mRNAs with 16 different 5'-untranslated regions (varying in length from 68 to 670 nucleotides) are produced from the 3-hydroxy-3-methylglutaryl coenzyme A reductase gene
SV40 gene expression is modulated by the cooperative binding of T antigen to DNA
TLDR
It is suggested that the cooperative binding of T antigen to its sites is directly responsible for inhibiting the initiation, rather than blocking elongation, of early RNA synthesis.
The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter
TLDR
Results suggest that direct binding of Sp 1 to sequences in the upstream promoter element is the mechanism by which this factor activates transcription by RNA polymerase II at the SV40 early promoter.
Amplification of the gene for 3-hydroxy-3-methylglutaryl coenzyme A reductase, but not for the 53-kDa protein, in UT-1 cells.
TLDR
It is concluded that the gene for 3-hydroxy-3-methylglutaryl coenzyme A reductase, but not for the 53-kDa protein, has been stably amplified in UT-1 cells.
Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth.
The availability of compactin (ML-236B), a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl Coenzyme A reductase, has permitted the demonstration of a hitherto unsuspected aspect of
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