Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocyte growth factor (HGF) is a multifunctional cytokine that controls the growth and differentiation of various tissues. Previously, we described the existence of a negative cis-acting regulatory element(s) within the -1- to -0.7-kilobase pair (kb) portion of the 5'-flanking region of the mouse HGF promoter. In the present study, we show that the repressor element is located at position -872 to -860 base pairs and comprises an imperfect estrogen-responsive element 5'-AGGTCAGAAAGACCA-3'. We demonstrate that chicken ovalbumin upstream promoter transcription factor (COUP-TF), a nuclear orphan receptor belonging to the steroid/thyroid hormone receptor superfamily, through binding to this site effectively silences the transcriptional activity of the HGF promoter. We show that estrogen receptor, on the other hand, relieves the repressive action of COUP-TF, resulting in the induction of the HGF promoter. Using mice transgenic for either 2.7 or 0.7 kb of the HGF promoter region linked to the chloramphenicol acetyltransferase reporter gene, we found that injection of estradiol stimulates HGF promoter activity in tissues such as the mammary gland and ovary of mice harboring 2.7 but not 0.7 kb of the mouse HGF promoter region. Potential involvement of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors in the regulation of HGF gene expression is also discussed.
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PMID:Transcriptional regulation of the hepatocyte growth factor gene by the nuclear receptors chicken ovalbumin upstream promoter transcription factor and estrogen receptor. 902 96

We have previously shown that COUP-TFII and Ear-2, two members of the nuclear orphan receptor family, are able to repress oestrogen-stimulated transcriptional activity of the human oxytocin (OT) gene promoter by binding to a site that overlaps with the oestrogen response element (ERE) present in the 5' flanking region of the gene. Although most nuclear receptor-mediated transcriptional repression conforms with the paradigm of passive repression and involves competitive binding to an activator site, active repression, i.e. silencing of basal promoter activity, has been observed in a limited number of cases. Here we show by co-transfection experiments using COUP-TFII and Ear-2 expression vectors and reporter constructs containing OT gene promoter fragments linked to the chloramphenicol acetyltransferase gene that both COUP-TFII and Ear-2 are capable of silencing basal OT gene promoter activity by 54 and 75% respectively. 5' Deletion and footprint analyses revealed two areas of functionally important interaction sites: (1) a direct TGACC(T/C) repeat overlapping the ERE and (2) a more promoter-proximal area centred at - 90 containing three imperfect direct repeats (R1-R3) spaced by four nucleotides each. Mutagenesis of reporter constructs as well as electrophoretic mobility-shift assays demonstrated that each of the three proximal repeats R1-R3 contributed to orphan receptor binding and the silencing effect. Inasmuch as the orphan receptor-binding sites are not involved in mediating basal transcriptional activity of the OT gene promoter, the observed effects are best interpreted as active repression or promoter silencing. Moreover, since COUP-TFII and Ear-2 are both co-expressed in OT-expressing uterine epithelial cells, the novel transcriptional effects described here are likely to be of functional importance in the fine-tuning of uterine OT gene expression in vivo.
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PMID:The nuclear orphan receptors COUP-TFII and Ear-2 act as silencers of the human oxytocin gene promoter. 934 8

Here, we analyzed the expression of the three members of the retinoid-like orphan receptor (ROR) nuclear receptor subfamily during adipocyte differentiation. RORalpha and RORgamma mRNA were upregulated during adipocyte differentiation in preadipocyte D1 and 3T3-L1 cells, whereas RORbeta mRNA could not be detected. The induction of RORalpha and RORgamma mRNA succeeded the induction of peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer binding protein alpha and occurred at a similar time interval as did the increase in aP2 and lipoprotein lipase mRNA. Like the expression of PPARgamma and aP2, the induction of RORgamma mRNA was repressed by tumor necrosis factor alpha and transforming growth factor beta. The induction of adipogenesis by prostaglandin D2 and two thiazolidinediones in the multipotent stem cells C3H10T1/2 was also accompanied by an induction in RORgamma mRNA. In contrast to parental cells, clofibrate induces adipogenesis and RORalpha and RORgamma mRNA in BALB/c3T3 cells that ectopically express PPARgamma. RORgamma mediates its effect on transcription through specific response elements. Cotransfection of RORalpha or RORgamma and (RORgamma response element)4-chloramphenicol acetyltransferase into preadipocyte D1 cells induced transactivation of chloramphenicol acetyltransferase about 100-fold, suggesting that ROR plays a role in the regulation of gene expression in adipocytes. The nuclear orphan receptor Rev-ErbAalpha, which did not exhibit transactivation function, was able to inhibit transactivation by RORgamma at two different levels. Our results show that RORgamma is induced during adipocyte differentiation in D1 and 3T3-L1 cells and functions as an active transcription factor, suggesting a role for RORgamma in the regulation of gene expression during this differentiation process.
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PMID:Induction of the nuclear orphan receptor RORgamma during adipocyte differentiation of D1 and 3T3-L1 cells. 954 93