Regulation of the Apolipoprotein AI Gene by ARP-1, a Novel Member of the Steroid Receptor Superfamily

Ladias, John A. A.; Karathanasis, Sotirios K.

doi:10.1126/science.1899293

Cited by 383 publications

(267 citation statements)

References 39 publications

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“…6). An excess of ARP-1 protein reduced the transcriptional activity of the wild-type Ϫ213CAT construct by 2-fold, a result consistent with the fact that ARP-1, when binding to its cognate sequence, usually exerts a repressor effect (28). As expected, an excess of ARP-1 protein had no effect in the absence of the ARP-1-binding site.…”

Section: Functional Assays To Test the Role Of The Footprints In Promsupporting

confidence: 83%

Characterization of Hepatic-specific Regulatory Elements in the Promoter Region of the Human Cholesterol 7α-Hydroxylase Gene

Cooper

Chen

Botelho-Yetkinler

et al. 1997

Journal of Biological Chemistry

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Cholesterol 7␣-hydroxylase is the rate-limiting enzyme in the degradation of cholesterol to bile salts and plays a central role in regulating cholesterol homeostasis. The mechanisms involved in the transcriptional control of the human gene are largely unknown. HepG2 cells represent an appropriate model system for the study of the regulation of the gene. To identify liverspecific DNA sequences in the promoter of the human CYP7 gene, we first examined the DNase I hypersensitivity in the 5 -region of the gene. An area of hypersensitivity was observed in the region from ؊50 to ؊200 of the human gene in nuclei from transcriptionally active HepG2 cells, but was absent in transcriptionally inactive HeLa cell nuclei or in free DNA. Various 5 -promoter deletion constructs were made and transfected into HepG2 cells. About 300 base pairs of upstream sequence are required for high level promoter activity of the human CYP7 gene in HepG2 cells. DNase I footprinting of the hypersensitive region revealed nine protected sequences. Gel retardation experiments demonstrated binding of HNF-3 to the segment from ؊80 to ؊70 and of hepatocyte nuclear factor HNF-4 (and ARP-1) to the segment from ؊148 to ؊127 of the human CYP7 promoter. Deletion of either of these sites depressed promoter activity in HepG2 cells. A third region from ؊313 to ؊285 is bound by members of the HNF-3 family and acts as an enhancer. Additionally, the segment from ؊197 to ؊173 binds a negative regulatory protein that is present in Chinese hamster ovary cell extracts and in HepG2 cell extracts. These experiments define the key control elements responsible for basal transcription of the human CYP7 gene in HepG2 cells.Cholesterol 7␣-hydroxylase catalyzes the rate-limiting step in the pathway that leads to the catabolism of cholesterol to bile acids (for review, see Ref. 1). Cholesterol 7␣-hydroxylase is a microsomal enzyme member of the cytochrome P-450 family. In human and rat, the major products of this metabolic pathway are cholic acid and chenodeoxycholic acid. Bile acids have an important role in cholesterol homeostasis; their synthesis and excretion cause a decrease in hepatic cholesterol levels, while their presence in the intestine facilitates the solubilization of dietary fats and is required for the absorption of cholesterol and fat-soluble vitamins. Because of the importance of these functions, bile acid synthesis in the liver is carefully regulated to maintain cholesterol homeostasis (1). To date, little is known about the molecular mechanisms that control cholesterol catabolism and bile acid synthesis.The cDNAs and genes for cholesterol 7␣-hydroxylase have been isolated from rat (2-4), human (5, 6), hamster (7), and mouse (8). CYP7 mRNA is found exclusively in the liver (9), making this gene a target for the study of the molecular mechanisms implicated in hepatic-specific gene expression. Work by several groups has demonstrated that CYP7 mRNA levels are modulated in cultured cells by a number of effectors. For example, in cultured rat hepatocytes (10) ...

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Section: Functional Assays To Test the Role Of The Footprints In Promsupporting

confidence: 83%

Characterization of Hepatic-specific Regulatory Elements in the Promoter Region of the Human Cholesterol 7α-Hydroxylase Gene

Cooper

Chen

Botelho-Yetkinler

et al. 1997

Journal of Biological Chemistry

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“…This correlates with the phase of active oxytocin transcription suggesting that the binding of the luteal protein might be an important step leading to activation of oxytocin transcription. The COUP-related factor, on the other hand, may play a role as negative regulator inhibiting transcription from the oxytocin promoter as has been described for the closely related transcription factor ARP-I in the regulation of the human apolipoprotein A1 gene (37).…”

Section: Discussionmentioning

confidence: 88%

Mapping of the Bovine Oxytocin Gene Control Region: Identification of Binding Sites for Luteal Nuclear Proteins in the 5′ Non‐Coding Region of the Gene

Walther¹,

Wehrenberg²,

Brackmann³

et al. 1991

J Neuroendocrinology

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In view of the small number of hormone-producing cells, the factors regulating oxytocin gene expression in the classic site of synthesis, in the magnocellular neurons of the hypothalamus, have not yet been characterized. In the early bovine corpus luteurn there is a tissue-specific oxytocin expression involving many more cells. This tissue therefore was chosen as a experimental system to identify deoxyribonucleic acid elements and nuclear proteins involved in the regulation of oxytocin gene expression. 3.2 kb from the 5' non-coding region of the bovine oxytocin gene have been sequenced and subcloned fragments used as probes for gel retardation and footprinting experiments. Binding sites for luteal as well as more ubiquitous proteins were detected in the oxytocin promoter region and in an artiodactyl-specific dispersed repeated deoxyribonucleic acid element. A binding site in the promoter region with a superficial similarity to an estrogen-responsive element (-159 to -152) was shown not to bind this steroid hormone receptor but to bind two nuclear proteins alternatively. One is a luteal protein, the other a more general transcription factor belonging to the steroid hormone receptor superfamily and similar, if not identical to the COUP protein. This alternative binding of a tissue-and phase-specifically expressed protein or an ubiquitous factor to the same site in the oxytocin promoter suggests a role for these two proteins in the transient up-regulation and subsequent down-regulation of the oxytocin gene during the differentiation of the bovine corpus luteum.

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“…Other binding sites for nuclear factors that are involved in gene response to various hormones are also located in the BamHI-XhoI region. The presence of two potential sequences for ARP1 binding, a novel member of the steroid receptor superfamily [57] and a potential thyroid-hormoneresponsive element (TRE), suggests that the expression of the chicken ACC gene could be modulated by hormones.…”

Section: Discussionmentioning

confidence: 99%

Cloning and characterization of the 5′ end and promoter region of the chicken acetyl-CoA carboxylase gene

Mounier

Fur

Powell

et al. 1996

Biochemical Journal

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Acetyl-CoA carboxylase is a rate-limiting enzyme in the biogenesis of long-chain fatty acids. In the present study, the 5h end and flanking region of the acetyl-CoA carboxylase (ACC) gene was analysed in the chicken. A genomic clone was isolated containing the first three exons, the third one containing the ATG codon. Using nuclease-mapping experiments and primerextension analyses, the transcription-initiation site was located 153 nucleotides upstream of the ATG codon. In contrast with rat ACC gene expression, reverse transcriptase PCR analysis performed on chicken liver mRNA did not reveal alternative splicing in the 5h-untranslated region of these messengers. The promoter

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Regulation of the Apolipoprotein AI Gene by ARP-1, a Novel Member of the Steroid Receptor Superfamily

Cited by 383 publications

References 39 publications

Characterization of Hepatic-specific Regulatory Elements in the Promoter Region of the Human Cholesterol 7α-Hydroxylase Gene

Characterization of Hepatic-specific Regulatory Elements in the Promoter Region of the Human Cholesterol 7α-Hydroxylase Gene

Mapping of the Bovine Oxytocin Gene Control Region: Identification of Binding Sites for Luteal Nuclear Proteins in the 5′ Non‐Coding Region of the Gene

Cloning and characterization of the 5′ end and promoter region of the chicken acetyl-CoA carboxylase gene

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